Anthelmintic quinoline-3-carboxamide derivatives

ABSTRACT

The present invention covers new quinoline compounds of general formula (I): 
                         
in which A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and Q are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 16/348,797, filed on May 9, 2019, which is a National StageApplication pursuant to 35 U.S.C. § 371 of International Application No.PCT/EP2017/078319, filed on Nov. 6, 2017, which claims the benefit ofEuropean Application No. 16198550.2, filed on Nov. 11, 2016.

The present invention covers new quinoline derivatives of generalformula (I) as described and defined herein, methods of preparing saidcompounds, intermediate compounds useful for preparing said compounds,pharmaceutical compositions and combinations comprising said compounds,and the use of said compounds for manufacturing pharmaceuticalcompositions for the control, treatment and/or prevention of diseases,in particular for the control, treatment and/or prevention of infectionswith helminths, more particularly of infections with gastro-intestinaland extra-intestinal nematodes, in animals and humans, formulationscontaining such compounds and methods for the control, treatment and/orprevention of infections with helminths, more particularly of infectionswith gastro-intestinal and extra-intestinal nematodes, in animals andhumans as a sole agent or in combination with other active ingredients.

BACKGROUND

The occurrence of resistances against all commercial anthelmintics seemsto be a growing problem in the area of veterinary medicine. Theextensive utilisation of anthelmintics to manage the control ofnematodes resulted in significant selection of highly resistant wormpopulations. Therefore, the spread of resistance against allanthelmintic drug classes threatens effective worm control in cattle,goats, sheep and horses. Furthermore, successful prevention of heartwormdisease in dogs, which currently solely relies on the utilisation ofmacrocyclic lactones, is in danger as loss of efficacy for multiplemacrocyclic lactones has been described for some regions of the UnitedStates of America—especially in those areas where the heartwormchallenge for infection is high. Finally, experimental infection studieswith Dirofilaria immitis larvae from suspected field loss of efficacycases in the Lower Mississippi Delta provided in vivo confirmation ofthe existence of macrocyclic lactone resistance.

Although resistance of human helminths against anthelmintics seemscurrently to be rare, the spread of anthelmintic resistance in theveterinary field as mentioned before needs to be considered in thetreatment of human helminthosis as well. Persistent underdosedtreatments against filariosis may lead to highly resistant genotypes andresistances have already been described for certain anthelmintics (e.g.praziquantel, benzimidazole and niclosamide).

Therefore, resistance-breaking anthelmintics with new molecular modes ofaction are urgently required.

It is an object of the present invention to provide compounds which canbe used as anthelmintics in the medical, especially veterinary, fieldwith a satisfactory or improved anthelmintic activity against a broadspectrum of helminths, particularly at relatively low dosages, for thecontrol, treatment and/or prevention of infections with helminths inanimals and humans, preferably without any adverse toxic effects to thetreated organism.

Certain quinoline carboxamides are described in JP2008-214323A as agentssuitable for treatment and/or prevention of skin diseases, like acnevulgaris, dermatitis or the like.

The WO2017103851 discloses quinoline-3-carboxamides as H-PGDSinhibitors, useful for treating atherosclerosis, psoriasis, sinusitis,and duchenne muscular dystrophy.

However, the state of the art does not describe the new quinolinederivatives of general formula (I) of the present invention as describedand defined herein.

It has now been found, and this constitutes the basis of the presentinvention, that the compounds of the present invention have surprisingand advantageous properties.

In particular, the compounds of the present invention have surprisinglybeen found to effectively interact with Slo-1 calcium-gated potassiumchannels of nematodes. This interaction is characterized by achievingparalysis/inhibition in particular of gastro-intestinal nematodes, offree-living nematodes, and of filariae, for which data are given in thebiological experimental section. Therefore the compounds of the presentinvention may be used as anthelmintics for the control, treatment and/orprevention of gastro-intestinal and extra-intestinal helminthinfections, in particular gastro-intestinal and extra-intestinalinfections with nematodes, including filariae.

DESCRIPTION OF THE INVENTION

In accordance with a first aspect, the present invention coverscompounds of general formula (I):

-   in which:-   A is A1 or A2,

o is 0, 1, 2, 3 or 4,

-   R is selected from the group consisting of hydrogen, halogen, cyano,    nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen    atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,    —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,    —S—C₁-C₄-halogenoalkyl, —S(O)—C₁-C₄-halogenoalkyl and    —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X, Y are independently selected from the group consisting of CR⁷R⁸,    O, S, and N—R⁹, wherein at least one of X and Y is CR⁷R⁸, or-   X, Y form together a ring member selected from the group consisting    of —C(O)—O—, —C(O)—NR⁹—, —S(O)—NR⁹—, —SO₂—NR⁹— and —SO₂—O—,-   R¹ is selected from the group consisting of hydrogen, cyano, —CHO,    —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    C₃-C₆-cycloalkyl, C₃-C₆-halogenocycloalkyl having 1 to 5 halogen    atoms, C₃-C₄-alkenyl, C₃-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,    C₃-C₆-cycloalkyl-C₁-C₃-alkyl, cyano-C₁-C₄-alkyl, —NH—C₁-C₄-alkyl,    —N(C₁-C₄-alkyl)₂, NH₂—C₁-C₄-alkyl-, C₁-C₄-alkyl-NH—C₁-C₄-alkyl-,    (C₁-C₄-alkyl)₂N—C₁-C₄-alkyl-, C₁-C₄-alkyl-C(O)—,    C₁-C₄-halogenoalkyl-C(O)— having 1 to 5 halogen atoms,    C₁-C₄-alkoxy-C(O)—, benzyloxy-C(O)—, C₁-C₄-alkoxy-C₁-C₄-alkyl-C(O)—,    —SC₂—C₁-C₄-alkyl, and —SC₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms;    -   phenyl-C₁-C₄-alkyl, optionally substituted by 1, 2, 3, 4 or 5        substituents independently selected from the group consisting of        halogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SC₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R² is selected from the group consisting of    -   hydrogen, halogen, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂;    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,        C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of        which is optionally substituted by 1, 2, 3, 4 or 5 substituents        independently selected from the group consisting of halogen,        —OH, —NO₂, cyano, C₁-C₄-alkyl-C(O)—, C₁-C₄-alkoxy-C(O)—,        —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH(C(O)—C₁-C₄-alkyl), —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl),        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SC₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SC₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SC₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SC₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl which is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to        5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to        5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and 4- to        10-membered heterocycloalkyl,-   R³ is hydrogen or C₁-C₄-alkyl,-   R⁴ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-halogenoalkyl having 1    to 5 halogen atoms, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₁-C₄-alkyl-C(O)—,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,    —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,-   R⁵ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-halogenoalkyl having 1    to 5 halogen atoms, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₁-C₄-alkyl-C(O)—,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,    —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,-   R⁶ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-halogenoalkyl having 1    to 5 halogen atoms, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₁-C₄-alkyl-C(O)—,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,    —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,-   R⁷ is selected from the group consisting of hydrogen, —OH, fluorine,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   R⁸ is selected from the group consisting of hydrogen, —OH, fluorine,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   or R⁷ and R⁸ together form an oxo group (═O),-   or R⁷ and R⁸ form, together with the carbon atom to which they are    attached, a 3- to 6-membered ring selected from the group consisting    of C₃-C₆-cycloalkyl and 3- to 6-membered heterocycloalkyl,-   R⁹ is selected from the group consisting of hydrogen, C₁-C₄-alkyl,    C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and C₁-C₄-alkoxy,-   R¹⁰ is selected from the group consisting of hydrogen, —OH,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   R¹¹ is selected from the group consisting of hydrogen, C₁-C₄-alkyl    and C₁-C₄-alkoxy,-   or R¹⁰ and R¹¹ form, together with the carbon atom to which they are    attached, a 3- to 6-membered ring selected from the group consisting    of C₃-C₆-cycloalkyl and 3- to 6-membered heterocycloalkyl,-   R¹² and R¹³ are independently selected from the group consisting of    hydrogen, —OH, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,    —NH(—C(O)—C₁-C₄-alkyl), —N(C₁-C₄-alkyl)(—C(O)—C₁-C₄-alkyl),    C₁-C₄-alkoxy, C₁-C₄-alkoxy-C(O)—;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        —NH—C(O)—C₁-C₄-alkyl, —N(C₁-C₄-alkyl)(—C(O)—C₁-C₄-alkyl),        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl, benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, nitro, —OH,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl, each of which is optionally substituted        by 1, 2 or 3 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substitutent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl, 5-membered        heteroaryl and 6-membered heteroaryl, each of which is        optionally substituted by 1, 2 or 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms; and a        monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl, 5-membered        heteroaryl and 6-membered heteroaryl, each of which is        optionally substituted by 1, 2 or 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   Q is selected from the group consisting of 6- or 10-membered aryl    and 5- to 10-membered heteroaryl, each of which is optionally    substituted by 1, 2, 3, 4 or 5 substituents selected from the group    consisting of halogen, SF₅, cyano, —CHO, nitro, oxo, C₁-C₄-alkyl,    C₁-C₄-hydroxyalkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    hydroxy, C₁-C₄-alkoxy, C₃-C₆-cycloalkyl-C₁-C₄-alkoxy,    cyano-C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen    atoms, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —NH—SO₂—(C₁-C₄-alkyl),    —N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl), (C₁-C₄-alkoxyimino)-C₁-C₄-alkyl,    4- to 6-membered heterocyclyl, which is optionally substituted with    1 or 2 substituents selected from the group consisting of fluorine,    chlorine, bromine, methyl and cyano, —CH₂—O—(C₁-C₄-alkyl),    —CH₂—NH(C₁-C₄-alkyl), —CH₂—N(C₁-C₄-alkyl)₂, methyl substituted with    a 4- to 6-membered heterocyclyl which itself is optionally    substituted with 1 or 2 substituents selected from the group    consisting of fluorine, chlorine, bromine, methyl and cyano,    —CH₂—S—(C₁-C₄-alkyl), —CH₂—S(O)—(C₁-C₄-alkyl),    —CH₂—SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-alkyl), —S(O)—(C₁-C₄-alkyl),    —SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen    atoms, —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,    —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,    —CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),    —NHCO(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-halogenoalkyl) having 1 to 5    halogen atoms,    wherein when Y is O, S or N—R⁹, none of R⁷, R⁸, R¹⁰ and R¹¹ is —OH,    and wherein when X is O, S or N—R⁹, none of R⁷ and R⁸ is —OH,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

Definitions

The term “substituted” means that one or more hydrogen atoms on thedesignated atom or group are replaced with a selection from theindicated group, provided that the designated atom's normal valencyunder the existing circumstances is not exceeded. Combinations ofsubstituents and/or variables are permissible.

The term “optionally substituted” means that the number of substituentscan be equal to or different from zero. Unless otherwise indicated, itis possible that optionally substituted groups are substituted with asmany optional substituents as can be accommodated by replacing ahydrogen atom with a non-hydrogen substituent on any available carbon ornitrogen atom. Commonly, it is possible for the number of optionalsubstituents, when present, to be 1, 2, 3, 4 or 5, in particular 1, 2 or3.

As used herein, the term “one or more”, e.g. in the definition of thesubstituents of the compounds of general formula (I) of the presentinvention, means “1, 2, 3, 4 or 5, particularly 1, 2, 3 or 4, moreparticularly 1, 2 or 3, even more particularly 1 or 2”.

As used herein, an oxo substituent represents an oxygen atom, which isbound to a carbon atom or to a sulfur atom via a double bond.

The term “ring substituent” means a substituent attached to an aromaticor nonaromatic ring which replaces an available hydrogen atom on thering.

Should a composite substituent be composed of more than one parts, e.g.(C₁-C₄-alkoxy)-(C₁-C₄-alkyl)-, it is possible for the position of agiven part to be at any suitable position of said composite substituent,i.e. the C₁-C₄-alkoxy part can be attached to any carbon atom of theC₁-C₄-alkyl part of said (C₁-C₄-alkoxy)-(C₁-C₄-alkyl)- group. A hyphenat the beginning or at the end of such a composite substituent indicatesthe point of attachment of said composite substituent to the rest of themolecule. Should a ring, comprising carbon atoms and optionally one ormore heteroatoms, such as nitrogen, oxygen or sulfur atoms for example,be substituted with a substituent, it is possible for said substituentto be bound at any suitable position of said ring, be it bound to asuitable carbon atom and/or to a suitable heteroatom.

As used herein, the position via which a respective substituent isconnected to the rest of the molecule may in a drawn structure bedepicted by a hash sign (#) or a dashed line in said substituent.

The term “comprising” when used in the specification includes“consisting of”.

If within the present text any item is referred to as “as mentionedherein”, it means that it may be mentioned anywhere in the present text.

The terms as mentioned in the present text have the following meanings:

The term “halogen atom” means a fluorine, chlorine, bromine or iodineatom, particularly a fluorine, chlorine or bromine atom.

The term “C₁-C₆-alkyl” means a linear or branched, saturated, monovalenthydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms. The term“C₁-C₄-alkyl” means a linear or branched, saturated, monovalenthydrocarbon group having 1, 2, 3, or 4 carbon atoms, e.g. a methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or a tert-butylgroup, or an isomer thereof. Particularly, said group has 1, 2 or 3carbon atoms (“C₁-C₃-alkyl”), e.g. a methyl, ethyl, n-propyl orisopropyl group.

The term “C₁-C₄-hydroxyalkyl” means a linear or branched, saturated,monovalent hydrocarbon group in which the term “C₁-C₄-alkyl” is definedsupra, and in which 1 or 2 hydrogen atoms are replaced with a hydroxygroup, e.g. a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl,1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl,1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl,2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl group.

The term “—NH(C₁-C₄-alkyl)” or “—N(C₁-C₄-alkyl)₂” means a linear orbranched, saturated, monovalent group in which the term “C₁-C₄-alkyl” isas defined supra, e.g. a methylamino, ethylamino, n-propylamino,isopropylamino, N,N-dimethylamino, N-methyl-N-ethylamino orN,N-diethylamino group.

The term “—S—C₁-C₄-alkyl”, “—S(O)—C₁-C₄-alkyl” or “—SO₂—C₁-C₄-alkyl”means a linear or branched, saturated group in which the term“C₁-C₄-alkyl” is as defined supra, e.g. a methylsulfanyl, ethylsulfanyl,n-propylsulfanyl, isopropylsulfanyl, n-butylsulfanyl, sec-butylsulfanyl,isobutylsulfanyl or tert-butylsulfanyl group, a methylsulfinyl,ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl,sec-butylsulfinyl, isobutylsulfinyl or tert-butylsulfinyl group, or amethylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl,n-butylsulfonyl, sec-butylsulfonyl, isobutylsulfonyl ortert-butylsulfonyl group.

The term “C₁-C₄-halogenoalkyl” means a linear or branched, saturated,monovalent hydrocarbon group in which the term “C₁-C₄-alkyl” is asdefined supra, and in which one or more of the hydrogen atoms arereplaced, identically or differently, with a halogen atom. Particularly,said halogen atom is a fluorine atom. More particularly, all saidhalogen atoms are fluorine atoms (“C₁-C₄-fluoroalkyl”). SaidC₁-C₄-halogenoalkyl group is, for example, fluoromethyl, difluoromethyl,trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,pentafluoroethyl, 3,3,3-trifluoropropyl or 1,3-difluoropropan-2-yl.

The term “C₁-C₄-alkoxy” means a linear or branched, saturated,monovalent group of formula (C₁-C₄-alkyl)-O—, in which the term“C₁-C₄-alkyl” is as defined supra, e.g. a methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy group, or anisomer thereof.

The term “C₁-C₄-halogenoalkoxy” means a linear or branched, saturated,monovalent C₁-C₄-alkoxy group, as defined supra, in which one or more ofthe hydrogen atoms is replaced, identically or differently, with ahalogen atom. Particularly, said halogen atom is a fluorine atom. SaidC₁-C₄-halogenoalkoxy group is, for example, fluoromethoxy,difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy orpentafluoroethoxy.

The term “C₂-C₄-alkenyl” means a linear or branched, monovalenthydrocarbon group, which contains one double bond, and which has 2, 3 or4 carbon atoms. Said C₂-C₄-alkenyl group is, for example, an ethenyl (or“vinyl”), a prop-2-en-1-yl (or “allyl”), prop-1-en-1-yl, but-3-enyl,but-2-enyl, but-1-enyl, prop-1-en-2-yl (or “isopropenyl”),2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl or a1-methylprop-1-enyl, group. Particularly, said group is allyl.

The term “C₂-C₄-alkynyl” means a linear monovalent hydrocarbon groupwhich contains one triple bond, and which contains 2, 3 or 4 carbonatoms. Said C₂-C₄-alkynyl group is, for example, an ethynyl, aprop-1-ynyl, prop-2-ynyl (or “propargyl”), but-1-ynyl, but-2-ynyl,but-3-ynyl or 1-methylprop-2-ynyl, group. Particularly, said alkynylgroup is prop-1-ynyl or prop-2-ynyl.

The term “C₃-C₆-cycloalkyl” means a saturated, monovalent, monocyclichydrocarbon ring which contains 3, 4, 5 or 6 carbon atoms(“C₃-C₆-cycloalkyl”). Said C₃-C₆-cycloalkyl group is for example, amonocyclic hydrocarbon ring, e.g. a cyclopropyl, cyclobutyl, cyclopentylor cyclohexyl group.

The term “C₃-C₆-halogenocycloalkyl” means a saturated, monovalent,monocyclic hydrocarbon ring in which the term “C₃-C₆-cycloalkyl” is asdefined supra, and in which one or more of the hydrogen atoms arereplaced, identically or differently, with a halogen atom. Particularly,said halogen atom is a fluorine or chlorine atom. SaidC₃-C₆-halogenocycloalkyl group is for example, a monocyclic hydrocarbonring substituted with one or two fluorine or chlorine atoms, e.g. a1-fluoro-cyclopropyl, 2-fluorocyclopropyl, 2,2-difluorocyclopropyl,2,3-difluorocyclopropyl, 1-chlorocyclopropyl, 2-chlorocyclopropyl,2,2-dichlorocyclopropyl, 2,3-dichlorocyclopropyl,2-fluoro-2-chlorocyclopropyl and 2-fluoro-3-chlorocyclopropyl group.

The term “benzo-C₅-C₆-cycloalkyl” means a monovalent, bicyclichydrocarbon ring wherein a saturated, monovalent, monocyclic hydrocarbonring which contains 5 or 6 carbon atoms (“C₅-C₆-cycloalkyl”) isannelated to a phenyl ring. Said benzo-C₅-C₆-cycloalkyl group is forexample, a bicyclic hydrocarbon ring, e.g. an indane (i.e.2,3-dihydro-1H-indene) or tetraline (i.e. 1,2,3,4-tetrahydronaphthalene)group.

The term “spirocycloalkyl” means a saturated, monovalent bicyclichydrocarbon group in which the two rings share one common ring carbonatom, and wherein said bicyclic hydrocarbon group contains 5, 6, 7, 8,9, 10 or 11 carbon atoms, it being possible for said spirocycloalkylgroup to be attached to the rest of the molecule via any one of thecarbon atoms except the spiro carbon atom. Said spirocycloalkyl groupis, for example, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[2.4]heptyl,spiro[2.5]octyl, spiro[2.6]nonyl, spiro[3.3]heptyl, spiro[3.4]octyl,spiro[3.5]nonyl, spiro[3.6]decyl, spiro[4.4]nonyl, spiro[4.5]decyl,spiro[4.6]undecyl or spiro[5.5]undecyl.

The term “heterocycloalkyl” means a monocyclic or bicyclic, saturated orpartially saturated heterocycle with 4, 5, 6, 7, 8, 9 or 10 ring atomsin total (a “4- to 10-membered heterocycloalkyl” group), particularly 4,5 or 6 ring atoms (a “4- to 6-membered heterocycloalkyl” group), whichcontains one or two identical or different ring heteroatoms from theseries N, O and S, it being possible for said heterocycloalkyl group tobe attached to the rest of the molecule via any one of the carbon atomsor, if present, a nitrogen atom.

Said heterocycloalkyl group, without being limited thereto, can be a4-membered ring, such as azetidinyl, oxetanyl or thietanyl, for example;or a 5-membered ring, such as tetrahydrofuranyl, oxolanyl,1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl,1,1-dioxidothiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl,1,3-thiazolidinyl or 1,2,4-triazolidinyl, for example; or a 6-memberedring, such as tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl,morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, oxanyl,1,3-dioxanyl, 1,4-dioxanyl or 1,2-oxazinanyl, for example; or a7-membered ring, such as azepanyl, 1,4-diazepanyl or 1,4-oxazepanyl, forexample; or a bicyclic 7-membered ring, such as6-oxa-3-azabicyclo[3.1.1]heptan, for example; or a bicyclic 8-memberedring, such as 5,6-dihydro-4H-furo[2,3-c]pyrrole or8-oxa-3-azabicyclo[3.2.1]octan, for example; or a bicyclic 9-memberedring, such as octahydro-1H-pyrrolo[3,4-b]pyridine, 1,3-dihydro-isoindol,2,3-dihydro-indol or 3,9-dioxa-7-azabicyclo[3.3.1]nonan, for example; ora bicyclic 10-membered ring, such as decahydroquinoline or3,4-dihydroisoquinolin, for example.

The term “heterospirocycloalkyl” means a bicyclic, saturated heterocyclewith 6, 7, 8, 9, 10 or 11 ring atoms in total, in which the two ringsshare one common ring carbon atom, which “heterospirocycloalkyl”contains one or two identical or different ring heteroatoms from theseries: N, O, S; it being possible for said heterospirocycloalkyl groupto be attached to the rest of the molecule via any one of the carbonatoms, except the spiro carbon atom, or, if present, a nitrogen atom.

Said heterospirocycloalkyl group is, for example, azaspiro[2.3]hexyl,azaspiro[3.3]heptyl, oxaazaspiro[3.3]heptyl, thiaazaspiro[3.3]heptyl,oxaspiro[3.3]heptyl, oxazaspiro[5.3]nonyl, oxazaspiro[4.3]octyl,oxaazaspiro[2.5]octyl, azaspiro[4.5]decyl, oxazaspiro[5.5]undecyl,diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl,azaspiro[5.5]undecyl, or one of the further homologous scaffolds such asspiro[3.4]-, spiro[4.4]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-,spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-.

The term “6- or 10-membered aryl” means a monovalent, monocyclic orbicyclic aromatic ring having 6 or 10 carbon ring atoms, e.g. a phenylor naphthyl group.

The term “heteroaryl” means a monovalent, monocyclic, bicyclic ortricyclic aromatic ring having 5, 6, 9 or 10 ring atoms (a “5- to10-membered heteroaryl” group), particularly 5 or 6 ring atoms (a “5- to6-membered heteroaryl” group), which contains at least one ringheteroatom and optionally one, two or three further ring heteroatomsfrom the series: N, O and/or S, and which is bound via a ring carbonatom or optionally via a ring nitrogen atom (if allowed by valency).

Said heteroaryl group can be a 5-membered heteroaryl group, such as, forexample, thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,thiadiazolyl or tetrazolyl; or a 6-membered heteroaryl group, such as,for example, pyridinyl, dihydropyridinyl, pyridazinyl, pyrimidinyl,tetrahydropyrimidinyl, pyrazinyl or triazinyl.

The term “heterocyclyl” means a heterocycle selected from the groupconsisting of heterocycloalkyl and heteroaryl. Particularly, the term“4- to 6-membered heterocyclyl” means a heterocycle selected from thegroup consisting of 4- to 6-membered heterocycloalkyl and 5- to6-membered heteroaryl.

In general, and unless otherwise mentioned, the heteroaryl orheteroarylene groups include all possible isomeric forms thereof, e.g.:tautomers and positional isomers with respect to the point of linkage tothe rest of the molecule. Thus, for some illustrative non-restrictingexamples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl andpyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl.

The term “C₁-C₄”, as used in the present text, e.g. in the context ofthe definition of “C₁-C₄-alkyl”, “C₁-C₄-halogenoalkyl”,“C₁-C₄-hydroxyalkyl”, “C₁-C₄-alkoxy” or “C₁-C₄-halogenoalkoxy” means analkyl group having a finite number of carbon atoms of 1 to 4, i.e. 1, 2,3 or 4 carbon atoms.

Further, as used herein, the term “C₃-C₆”, as used in the present text,e.g. in the context of the definition of “C₃-C₆-cycloalkyl” orC₃-C₆-halogenocycloalkyl, means a cycloalkyl group having a finitenumber of carbon atoms of 3 to 6, i.e. 3, 4, 5 or 6 carbon atoms.

When a range of values is given, said range encompasses each value andsub-range within said range.

For example:

“C₁-C₄” encompasses C₁, C₂, C₃, C₄, C₁-C₄, C₁-C₃, C₁-C₂, C₂-C₄, C₂-C₃,and C₃-C₄;

“C₂-C₆” encompasses C₂, C₃, C₄, C₅, C₆, C₂-C₆, C₂-C₅, C₂-C₄, C₂-C₃,C₃-C₆, C₃-C₅, C₃-C₄, C₄-C₆, C₄-C₅, and C₅-C₆;

“C₃-C₄” encompasses C₃, C₄, and C₃-C₄;

“C₃-C₁₀” encompasses C₃, C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₃-C₁₀, C₃-C₉,C₃-C₈, C₃-C₇, C₃-C₆, C₃-C₅, C₃-C₄, C₄-C₁₀, C₄-C₉, C₄-C₈, C₄-C₇, C₄-C₆,C₄-C₅, C₅-C₁₀, C₅-C₉, C₅-C₈, C₅-C₇, C₅-C₆, C₆-C₁₀, C₆-C₉, C₆-C₈, C₆-C₇,C₇-C₁₀, C₇-C₉, C₇-C₈, C₈-C₁₀, C₈-C₉ and C₉-C₁₀;

“C₃-C₈” encompasses C₃, C₄, C₅, C₆, C₇, C₈, C₃-C₈, C₃-C₇, C₃-C₆, C₃-C₅,C₃-C₄, C₄-C₈, C₄-C₇, C₄-C₆, C₄—O₅, C₅-C₈, C₅-C₇, C₅-C₆, C₆-C₈, C₆-C₇ andC₇-C₈;

“C₃-C₆” encompasses C₃, C₄, C₅, C₆, C₃-C₆, C₃-C₅, C₃-C₄, C₄-C₆, C₄-C₅,and C₅-C₆;

“C₄-C₈” encompasses C₄, C₅, C₆, C₇, C₈, C₄-C₈, C₄-C₇, C₄-C₆, C₄-C₅,C₅-C₈, C₅-C₇, C₅-C₆, C₆-C₈, C₆-C₇ and C₇-C₈;

“C₄-C₇” encompasses C₄, C₅, C₆, C₇, C₄-C₇, C₄-C₆, C₄-C₅, C₅-C₇, C₅-C₆and C₆-C₇;

“C₄-C₆” encompasses C₄, C₅, C₆, C₄-C₆, C₄-05 and C₅-C₆;

“C₅-C₁₀” encompasses C₅, C₆, C₇, C₈, C₉, C₁₀, C₅-C₁₀, C₅-C₉, C₅-C₈,C₅-C₇, C₅-C₆, C₆-C₁₀, C₆-C₉, C₆-C₈, C₆-C₇, C₇-C₁₀, C₇-C₉, C₇-C₈, C₈-C₁₀,C₈-C₉ and C₈-C₁₀;

“C₆-C₁₀” encompasses C₆, C₇, C₈, C₉, C₁₀, C₆-C₁₀, C₆-C₉, C₆-C₈, C₆-C₇,C₇-C₁₀, C₇-C₉, C₇-C₈, C₈-C₁₀, C₈-C₉ and C₉-C₁₀.

As used herein, the term “leaving group” means an atom or a group ofatoms that is displaced in a chemical reaction as stable species takingwith it the bonding electrons. In particular, such a leaving group isselected from the group comprising: halide, in particular fluoride,chloride, bromide or iodide, (methylsulfonyl)oxy,[(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)-sulfonyl]oxy,(phenylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy,[(4-bromophenyl)sulfonyl]oxy, [(4-nitrophenyl)sulfonyl]oxy,[(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy,[(2,4,6-triisopropylphenyl)sulfonyl]oxy,[(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butyl-phenyl)sulfonyl]oxyand [(4-methoxyphenyl)sulfonyl]oxy.

An oxo substituent in the context of the invention means an oxygen atom,which is bound to a carbon atom via a double bond.

It is possible for the compounds of general formula (I) to exist asisotopic variants. The invention therefore includes one or more isotopicvariant(s) of the compounds of general formula (I), particularlydeuterium-containing compounds of general formula (I).

The term “Isotopic variant” of a compound or a reagent is defined as acompound exhibiting an unnatural proportion of one or more of theisotopes that constitute such a compound.

The term “Isotopic variant of the compound of general formula (I)” isdefined as a compound of general formula (I) exhibiting an unnaturalproportion of one or more of the isotopes that constitute such acompound.

The expression “unnatural proportion” means a proportion of such isotopewhich is higher than its natural abundance. The natural abundances ofisotopes to be applied in this context are described in “IsotopicCompositions of the Elements 1997”, Pure Appl. Chem., 70(1), 217-235,1998.

Examples of such isotopes include stable and radioactive isotopes ofhydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine,chlorine, bromine and iodine, such as ²H (deuterium), ³H (tritium), ¹¹C,¹³C, ¹⁴C, ¹⁵N, ¹⁷O, ¹⁸O, ³²P, ³³P, ³³S, ³⁴S, ³⁵S, ³⁶S, ¹⁸F, ³⁶Cl, ⁸²Br,¹²³I, ¹²⁴I, ¹²⁵I, ¹²⁹I and ¹³¹I, respectively.

With respect to the treatment and/or prevention of the disordersspecified herein the isotopic variant(s) of the compounds of generalformula (I) preferably contain deuterium (“deuterium-containingcompounds of general formula (I)”). Isotopic variants of the compoundsof general formula (I) in which one or more radioactive isotopes, suchas ³H or ¹⁴C, are incorporated are useful e.g. in drug and/or substratetissue distribution studies. These isotopes are particularly preferredfor the ease of their incorporation and detectability. Positron emittingisotopes such as ¹⁸F or ¹¹C may be incorporated into a compound ofgeneral formula (I). These isotopic variants of the compounds of generalformula (I) are useful for in vivo imaging applications.Deuterium-containing and ¹³C-containing compounds of general formula (I)can be used in mass spectrometry analyses in the context of preclinicalor clinical studies.

Isotopic variants of the compounds of general formula (I) can generallybe prepared by methods known to a person skilled in the art, such asthose described in the schemes and/or examples herein, by substituting areagent for an isotopic variant of said reagent, preferably for adeuterium-containing reagent. Depending on the desired sites ofdeuteration, in some cases deuterium from D₂O can be incorporated eitherdirectly into the compounds or into reagents that are useful forsynthesizing such compounds. Deuterium gas is also a useful reagent forincorporating deuterium into molecules. Catalytic deuteration ofolefinic bonds and acetylenic bonds is a rapid route for incorporationof deuterium. Metal catalysts (i.e. Pd, Pt, and Rh) in the presence ofdeuterium gas can be used to directly exchange deuterium for hydrogen infunctional groups containing hydrocarbons. A variety of deuteratedreagents and synthetic building blocks are commercially available fromcompanies such as for example C/D/N Isotopes, Quebec, Canada; CambridgeIsotope Laboratories Inc., Andover, Mass., USA; and CombiPhos Catalysts,Inc., Princeton, N.J., USA.

The term “deuterium-containing compound of general formula (I)” isdefined as a compound of general formula (I), in which one or morehydrogen atom(s) is/are replaced by one or more deuterium atom(s) and inwhich the abundance of deuterium at each deuterated position of thecompound of general formula (I) is higher than the natural abundance ofdeuterium, which is about 0.015%. Particularly, in adeuterium-containing compound of general formula (I) the abundance ofdeuterium at each deuterated position of the compound of general formula(I) is higher than 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80%, preferablyhigher than 90%, 95%, 96% or 97%, even more preferably higher than 98%or 99% at said position(s). It is understood that the abundance ofdeuterium at each deuterated position is independent of the abundance ofdeuterium at other deuterated position(s).

The selective incorporation of one or more deuterium atom(s) into acompound of general formula (I) may alter the physicochemical properties(such as for example acidity [C. L. Perrin, et al., J. Am. Chem. Soc.,2007, 129, 4490], basicity [C. L. Perrin et al., J. Am. Chem. Soc.,2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984,19(3), 271]) and/or the metabolic profile of the molecule and may resultin changes in the ratio of parent compound to metabolites or in theamounts of metabolites formed. Such changes may result in certaintherapeutic advantages and hence may be preferred in some circumstances.Reduced rates of metabolism and metabolic switching, where the ratio ofmetabolites is changed, have been reported (A. E. Mutlib et al.,Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in theexposure to parent drug and metabolites can have important consequenceswith respect to the pharmacodynamics, tolerability and efficacy of adeuterium-containing compound of general formula (I). In some casesdeuterium substitution reduces or eliminates the formation of anundesired or toxic metabolite and enhances the formation of a desiredmetabolite (e.g. Nevirapine: A. M. Sharma et al., Chem. Res. Toxicol.,2013, 26, 410; Efavirenz: A. E. Mutlib et al., Toxicol. Appl.Pharmacol., 2000, 169, 102). In other cases the major effect ofdeuteration is to reduce the rate of systemic clearance. As a result,the biological half-life of the compound is increased. The potentialclinical benefits would include the ability to maintain similar systemicexposure with decreased peak levels and increased trough levels. Thiscould result in lower side effects and enhanced efficacy, depending onthe particular compound's pharmacokinetic/pharmacodynamic relationship.ML-337 (C. J. Wenthur et al., J. Med. Chem., 2013, 56, 5208) andOdanacatib (K. Kassahun et al., WO2012/112363) are examples for thisdeuterium effect. Still other cases have been reported in which reducedrates of metabolism result in an increase in exposure of the drugwithout changing the rate of systemic clearance (e.g. Rofecoxib: F.Schneider et al., Arzneim. Forsch./Drug. Res., 2006, 56, 295;Telaprevir: F. Maltais et al., J. Med. Chem., 2009, 52, 7993).Deuterated drugs showing this effect may have reduced dosingrequirements (e.g. lower number of doses or lower dosage to achieve thedesired effect) and/or may produce lower metabolite loads.

A compound of general formula (I) may have multiple potential sites ofattack for metabolism. To optimize the above-described effects onphysicochemical properties and metabolic profile, deuterium-containingcompounds of general formula (I) having a certain pattern of one or moredeuterium-hydrogen exchange(s) can be selected. Particularly, thedeuterium atom(s) of deuterium-containing compound(s) of general formula(I) is/are attached to a carbon atom and/or is/are located at thosepositions of the compound of general formula (I), which are sites ofattack for metabolizing enzymes such as e.g. cytochrome P₄₅₀.

Where the plural form of the word compounds, salts, polymorphs,hydrates, solvates and the like, is used herein, this is taken to meanalso a single compound, salt, polymorph, isomer, hydrate, solvate or thelike.

By “stable compound’ or “stable structure” is meant a compound that issufficiently robust to survive isolation to a useful degree of purityfrom a reaction mixture, and formulation into an efficacious therapeuticagent.

The compounds of the present invention optionally contain one or moreasymmetric centres, depending upon the location and nature of thevarious substituents desired. It is possible that one or more asymmetriccarbon atoms are present in the (R) or (S) configuration, which canresult in racemic mixtures in the case of a single asymmetric centre,and in diastereomeric mixtures in the case of multiple asymmetriccentres. In certain instances, it is possible that asymmetry also bepresent due to restricted rotation about a given bond, for example, thecentral bond adjoining two substituted aromatic rings of the specifiedcompounds.

Preferred compounds are those which produce the more desirablebiological activity. Separated, pure or partially purified isomers andstereoisomers or racemic or diastereomeric mixtures of the compounds ofthe present invention are also included within the scope of the presentinvention. The purification and the separation of such materials can beaccomplished by standard techniques known in the art.

Preferred isomers are those which produce the more desirable biologicalactivity. These separated, pure or partially purified isomers or racemicmixtures of the compounds of this invention are also included within thescope of the present invention. The purification and the separation ofsuch materials can be accomplished by standard techniques known in theart.

The optical isomers can be obtained by resolution of the racemicmixtures according to conventional processes, for example, by theformation of diastereoisomeric salts using an optically active acid orbase or formation of covalent diastereomers. Examples of appropriateacids are tartaric, diacetyltartaric, ditoluoyltartaric andcamphorsulfonic acid. Mixtures of diastereoisomers can be separated intotheir individual diastereomers on the basis of their physical and/orchemical differences by methods known in the art, for example, bychromatography or fractional crystallisation. The optically active basesor acids are then liberated from the separated diastereomeric salts. Adifferent process for separation of optical isomers involves the use ofchiral chromatography (e.g., HPLC columns using a chiral phase), with orwithout conventional derivatisation, optimally chosen to maximise theseparation of the enantiomers. Suitable HPLC columns using a chiralphase are commercially available, such as those manufactured by Daicel,e.g., Chiracel OD and Chiracel OJ, for example, among many others, whichare all routinely selectable. Enzymatic separations, with or withoutderivatisation, are also useful. The optically active compounds of thepresent invention can likewise be obtained by chiral syntheses utilizingoptically active starting materials.

In order to distinguish different types of isomers from each otherreference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11-30,1976).

The present invention includes all possible stereoisomers of thecompounds of the present invention as single stereoisomers, or as anymixture of said stereoisomers, e.g. (R)- or (S)-isomers, in any ratio.Isolation of a single stereoisomer, e.g. a single enantiomer or a singlediastereomer, of a compound of the present invention is achieved by anysuitable state of the art method, such as chromatography, especiallychiral chromatography, for example.

Further, it is possible for the compounds of the present invention toexist as tautomers. For example, any compound of the present inventionwhich contains a substitution pattern resulting in α-CH-moiety at thequinoline that has an increased C—H-acidity can exist as a1,4-dihydroquinoline tautomer, or even a mixture in any amount of thetwo tautomers, namely:

The present invention includes all possible tautomers of the compoundsof the present invention as single tautomers, or as any mixture of saidtautomers, in any ratio.

Further, the compounds of the present invention can exist as N-oxides,which are defined in that at least one nitrogen of the compounds of thepresent invention is oxidised. The present invention includes all suchpossible N-oxides.

The present invention also covers useful forms of the compounds of thepresent invention, such as metabolites, hydrates, solvates, prodrugs,salts, in particular pharmaceutically acceptable salts, and/orco-precipitates.

The compounds of the present invention can exist as a hydrate, or as asolvate, wherein the compounds of the present invention contain polarsolvents, in particular water, methanol or ethanol for example, asstructural element of the crystal lattice of the compounds. It ispossible for the amount of polar solvents, in particular water, to existin a stoichiometric or non-stoichiometric ratio. In the case ofstoichiometric solvates, e.g. a hydrate, hemi-, (semi-), mono-, sesqui-,di-, tri-, tetra-, penta- etc. solvates or hydrates, respectively, arepossible. The present invention includes all such hydrates or solvates.

Further, it is possible for the compounds of the present invention toexist in free form, e.g. as a free base, or as a free acid, or as azwitterion, or to exist in the form of a salt. Said salt may be anysalt, either an organic or inorganic addition salt, particularly anypharmaceutically acceptable organic or inorganic addition salt, which iscustomarily used in pharmacy, or which is used, for example, forisolating or purifying the compounds of the present invention.

The term “pharmaceutically acceptable salt” refers to an inorganic ororganic acid addition salt of a compound of the present invention. Forexample, see S. M. Berge, et al. “Pharmaceutical Salts,” J. Pharm. Sci.1977, 66, 1-19.

A suitable pharmaceutically acceptable salt of the compounds of thepresent invention may be, for example, an acid-addition salt of acompound of the present invention bearing a nitrogen atom, in a chain orin a ring, for example, which is sufficiently basic, such as anacid-addition salt with an inorganic acid, or “mineral acid”, such ashydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, bisulfuric,phosphoric, or nitric acid, for example, or with an organic acid, suchas formic, acetic, acetoacetic, pyruvic, trifluoroacetic, propionic,butyric, hexanoic, heptanoic, undecanoic, lauric, benzoic, salicylic,2-(4-hydroxybenzoyl)-benzoic, camphoric, cinnamic,cyclopentanepropionic, digluconic, 3-hydroxy-2-naphthoic, nicotinic,pamoic, pectinic, 3-phenylpropionic, pivalic, 2-hydroxyethanesulfonic,itaconic, trifluoromethanesulfonic, dodecylsulfuric, ethanesulfonic,benzenesulfonic, para-toluenesulfonic, methanesulfonic,2-naphthalenesulfonic, naphthalinedisulfonic, camphorsulfonic acid,citric, tartaric, stearic, lactic, oxalic, malonic, succinic, malic,adipic, alginic, maleic, fumaric, D-gluconic, mandelic, ascorbic,glucoheptanoic, glycerophosphoric, aspartic, sulfosalicylic, orthiocyanic acid, for example.

Further, another suitably pharmaceutically acceptable salt of a compoundof the present invention which is sufficiently acidic, is an alkalimetal salt, for example a sodium or potassium salt, an alkaline earthmetal salt, for example a calcium, magnesium or strontium salt, or analuminium or a zinc salt, or an ammonium salt derived from ammonia orfrom an organic primary, secondary or tertiary amine having 1 to 20carbon atoms, such as ethylamine, diethylamine, triethylamine,ethyldiisopropylamine, monoethanolamine, diethanolamine,triethanolamine, dicyclohexylamine, dimethylaminoethanol,diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine,dibenzylamine, N-methylmorpholine, arginine, lysine,1,2-ethylenediamine, N-methylpiperidine, N-methyl-glucamine,N,N-dimethyl-glucamine, N-ethyl-glucamine, 1,6-hexanediamine,glucosamine, sarcosine, serinol, 2-amino-1,3-propanediol,3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol, or a salt with aquanternary ammonium ion having 1 to 20 carbon atoms, such astetramethylammonium, tetraethylammonium, tetra(n-propyl)ammonium,tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline orbenzalkonium.

Those skilled in the art will further recognise that it is possible foracid addition salts of the claimed compounds to be prepared by reactionof the compounds with the appropriate inorganic or organic acid via anyof a number of known methods. Alternatively, alkali and alkaline earthmetal salts of acidic compounds of the present invention are prepared byreacting the compounds of the present invention with the appropriatebase via a variety of known methods.

The present invention includes all possible salts of the compounds ofthe present invention as single salts, or as any mixture of said salts,in any ratio.

In the present text, in particular in the Experimental Section, for thesynthesis of intermediates and of examples of the present invention,when a compound is mentioned as a salt form with the corresponding baseor acid, the exact stoichiometric composition of said salt form, asobtained by the respective preparation and/or purification process, is,in most cases, unknown.

Unless specified otherwise, suffixes to chemical names or structuralformulae relating to salts, such as “hydrochloride”, “trifluoroacetate”,“sodium salt”, or “x HCl”, “x CF₃COOH”, “x Na⁺”, for example, mean asalt form, the stoichiometry of which salt form not being specified.

This applies analogously to cases in which synthesis intermediates orexample compounds or salts thereof have been obtained, by thepreparation and/or purification processes described, as solvates, suchas hydrates, with (if defined) unknown stoichiometric composition.

Furthermore, the present invention includes all possible crystallineforms, or polymorphs, of the compounds of the present invention, eitheras single polymorph, or as a mixture of more than one polymorph, in anyratio.

Moreover, the present invention also includes prodrugs of the compoundsaccording to the invention. The term “prodrugs” here designatescompounds which themselves can be biologically active or inactive, butare converted (for example metabolically or hydrolytically) intocompounds according to the invention during their residence time in thebody.

In accordance with a second embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0, 1, 2, 3 or 4,-   R is selected from the group consisting of hydrogen, halogen, cyano,    nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen    atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,    —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,    —S—C₁-C₄-halogenoalkyl, —S(O)—C₁-C₄-halogenoalkyl and    —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X, Y are independently selected from the group consisting of CR⁷R⁸,    O, S, and N—R⁹, wherein at least one of X and Y is CR⁷R⁸, or-   X, Y form together a ring member selected from the group consisting    of —C(O)—O—, —C(O)—NR⁹—, —S(O)—NR⁹—, —SO₂—NR⁹— and —SO₂—O—,-   R¹ is selected from the group consisting of hydrogen, cyano, —CHO,    —OH, C₁-C₄-alkyl, C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄alkoxy, C₁-C₄halogenoalkoxy having 1 to 5 halogen atoms,    C₃-C₆-cycloalkyl, C₃-C₆-halogenocycloalkyl having 1 to 5 halogen    atoms, C₃-C₄alkenyl, C₃-C₄alkynyl, C₁-C₄alkoxy-C₁-C₄alkyl,    C₃-C₆-cycloalkyl-cyano-C₁-C₄alkyl, —NH—C₁-C₄-alkyl, —N(C₁-C₄alkyl)₂,    NH₂—C₁-C₄alkyl-, C₄-alkyl-NH—C₁-C₄alkyl-,    (C₁-C₄alkyl)₂N—C₁-C₄alkyl-, C₁-C₄-halogenoalkyl-C(O)— having 1 to 5    halogen atoms, C₁-C₄alkoxy-C(O)—, benzyloxy-C(O)—,    C₁-C₄alkoxy-C₁-C₄alkyl-C(O)—, —SO₂—C₁-C₄alkyl, and    —SO₂—C₁-C₄halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl-C₁-C₄-alkyl, optionally substituted by 1, 2, 3, 4 or 5        substituents independently selected from the group consisting of        halogen, —OH, —NO₂, cyano, C₁-C₄halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄alkoxy, C₁-C₄halogenoalkoxy having 1 to 5        halogen atoms, —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₄alkyl)₂,        —SO₂—C₁-C₄alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄alkoxy, C₁-C₄halogenoalkoxy having 1 to 5        halogen atoms, —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₄alkyl)₂,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄halogenoalkyl having 1 to 5        halogen atoms,-   R² is selected from the group consisting of    -   hydrogen, halogen, cyano, —COOH, C₁-C₄alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄alkyl)₂,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,        C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of        which is optionally substituted by 1, 2, 3, 4 or 5 substituents        independently selected from the group consisting of halogen,        —OH, —NO₂, cyano, C₁-C₄-alkyl-C(O)—, C₁-C₄-alkoxy-C(O)—,        —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH(C(O)—C₁-C₄-alkyl), —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl),        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SC₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SC₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SC₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SC₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl which is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to        5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to        5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and 4- to        10-membered heterocycloalkyl,-   R³ is hydrogen, or C₁-C₄-alkyl,-   R⁴ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,-   R⁵ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,-   R⁶ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,-   R⁷ is selected from the group consisting of hydrogen, —OH, fluorine,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   R⁸ is selected from the group consisting of hydrogen, —OH, fluorine,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   or R⁷ and R⁸ together form an oxo group (═O),-   R⁹ is selected from the group consisting of hydrogen, C₁-C₄-alkyl,    C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and C₁-C₄-alkoxy,-   R¹⁰ is selected from the group consisting of hydrogen, —OH,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   R¹¹ is selected from the group consisting of hydrogen, C₁-C₄-alkyl    and C₁-C₄-alkoxy,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —OH, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        —NH—C(O)—C₁-C₄-alkyl, —N(C₁-C₄-alkyl)-(—C(O)—C₁-C₄-alkyl),        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄alkyl, C₁-C₄halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₄alkyl)₂,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl, benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, nitro, —OH,        C₁-C₄alkyl, C₁-C₄halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄alkoxy, C₁-C₄halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄alkyl)₂,        —SO₂—C₁-C₄alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄halogenoalkyl having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl, each of which is optionally substituted        by 1, 2 or 3 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄alkyl),        —C(O)—N(C₁-C₄alkyl)₂, C₁-C₄alkyl, C₁-C₄halogenoalkyl having 1 to        5 halogen atoms, C₁-C₄alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₄alkyl)₂,        —SO₂—C₁-C₄alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₄alkyl)₂;    -   C₁-C₄alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄alkyl,        C₁-C₄halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄alkoxy,        C₁-C₄halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄alkyl)₂,        —SO₂—C₁-C₄alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substitutent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl, 5-membered        heteroaryl and 6-membered heteroaryl, each of which is        optionally substituted by 1, 2 or 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁—C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, oxo, thiono, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms;    -   phenyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl, 5-membered        heteroaryl and 6-membered heteroaryl, each of which is        optionally substituted by 1, 2 or 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,        —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹, Z², Z³, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, SF₅, cyano, —CHO, nitro,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        hydroxy, C₁-C₄-alkoxy, C₃-C₆-cycloalkyl-C₁-C₄-alkoxy,        cyano-C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH—SO₂—(C₁-C₄-alkyl), —N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl),        (C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4- to 6-membered heterocyclyl,        which is optionally substituted with 1 or 2 substituents        selected from the group consisting of fluorine, chlorine,        bromine, methyl and cyano, —CH₂—O—(C₁-C₄-alkyl),        —CH₂—NH(C₁-C₄-alkyl), —CH₂—N(C₁-C₄-alkyl)₂, methyl substituted        with a 4- to 6-membered heterocyclyl which itself is optionally        substituted with 1 or 2 substituents selected from the group        consisting of fluorine, chlorine, bromine, methyl and cyano,        —CH₂—S—(C₁-C₄-alkyl), —CH₂—S(O)—(C₁-C₄-alkyl),        —CH₂—SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-alkyl), —S(O)—(C₁-C₄-alkyl),        —SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-halogenoalkyl) having 1 to 5        halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen        atoms, —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),        —NHCO(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-halogenoalkyl) having 1 to        5 halogen atoms, or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5- or 6-membered saturated or partially        saturated heterocyclic ring, a 5-membered heteroaryl, or a        6-membered heteroaryl, each of which may be optionally        substituted with one or two substituents selected from the group        consisting of methyl, fluorine and oxo, and    -   Z³, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, SF₅, cyano, CHO, nitro,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        hydroxy, C₁-C₄-alkoxy, C₃-C₆-cycloalkyl-C₁-C₄-alkoxy,        cyano-C₁-C₄-alkoxy, C₁-C₄-alkoxy-C(O)—, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH—SO₂—(C₁-C₄-alkyl), —N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl),        (C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4- to 6-membered        heterocycloalkyl which is optionally substituted with 1 or 2        substituents selected from the group consisting of fluorine,        methyl or cyano, —CH₂—O—(C₁-C₄-alkyl), —CH₂—NH(C₁-C₄-alkyl),        —CH₂—N(C₁-C₄-alkyl)₂, methyl substituted with a 4- to 6-membered        heterocycloalkyl which itself is optionally substituted with 1        or 2 substituents selected from the group consisting of        fluorine, methyl or cyano, —CH₂—S—(C₁-C₄-alkyl),        —CH₂—S(O)—(C₁-C₄-alkyl), —CH₂—SO₂—(C₁-C₄-alkyl),        —S—(C₁-C₄-alkyl), —S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl),        —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),        —NHCO(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-halogenoalkyl) having 1 to        5 halogen atoms, or    -   Z² and Z³ form, together with the carbon atoms that they are        connected to, a 5- or 6-membered saturated or partially        saturated heterocyclic ring, a 5-membered heteroaryl, or a        6-membered heteroaryl, each of which may be optionally        substituted with one or two substituents selected from the group        consisting of methyl, fluorine and oxo, and    -   Z¹, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, SF₅, cyano, CHO, nitro,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        hydroxy, C₁-C₄-alkoxy, C₃-C₆-cycloalkyl-C₁-C₄-alkoxy,        cyano-C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH—SO₂—(C₁-C₄-alkyl), —N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl),        (C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4- to 6-membered        heterocycloalkyl which is optionally substituted with 1 or 2        substituents selected from the group consisting of fluorine,        methyl or cyano, —CH₂—O—(C₁-C₄-alkyl), —CH₂—NH(C₁-C₄-alkyl),        —CH₂—N(C₁-C₄-alkyl)₂, methyl substituted with a 4- to 6-membered        heterocycloalkyl which itself is optionally substituted with 1        or 2 substituents selected from the group consisting of        fluorine, methyl or cyano, —CH₂—S—(C₁-C₄-alkyl),        —CH₂—S(O)—(C₁-C₄-alkyl), —CH₂—SO₂—(C₁-C₄-alkyl),        —S—(C₁-C₄-alkyl), —S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl),        —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),        —NHCO(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-halogenoalkyl) having 1 to        5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q2)

-   -   in which:    -   Z⁶, Z⁷, Z⁹ and Z⁹ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a pyrimidine ring of the formula (Q3)

-   -   in which:    -   Z¹⁰, Z¹¹ and Z¹² are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH—CO—C₁-C₄-alkyl, and monocyclic heterocycles selected from        the group of 4- to 7-membered heterocycloalkyl or 5-membered        heteroaryls having at least one nitrogen atom via which the        heteroaryl ring is connected to the pyridine ring, each of which        is optionally substituted with 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, —OH, oxo, thiono, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—(C₁-C₄-halogenoalkyl)        having 1 to 5 halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having        1 to 5 halogen atoms, —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5        halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, Z¹⁹ and Z²⁰ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms,        wherein when Y is O, S or N—R⁹, none of R⁷, R⁸, R¹⁰ and R¹¹ is        —OH, and wherein when X is O, S or N—R⁹, none of R⁷ and R⁸ is        —OH,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In accordance with a third embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0, 1 or 2,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy, cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X, Y are independently selected from the group consisting of CR⁷R⁸,    O, S, and N—R⁹, wherein at least one of X and Y is CR⁷R⁸,-   R¹ is selected from the group consisting of hydrogen, C₁-C₄-alkyl,    C₃-C₆-cycloalkyl, C₃-C₄-alkenyl, C₃-C₄-alkynyl,    C₁-C₄-alkoxy-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-C₁-C₃-alkyl,    cyano-C₁-C₄-alkyl,-   R² is selected from the group consisting of    -   hydrogen, halogen, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂;    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,        C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of        which is optionally substituted by 1, 2, 3, 4 or 5 substituents        independently selected from the group consisting of halogen,        —OH, cyano, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —NH(C(O)—C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, cyano, —OH, oxo, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, and        4- to 10-membered heterocycloalkyl,-   R³ is hydrogen or C₁-C₄-alkyl,-   R⁴ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,-   R⁵ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,-   R⁶ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁹ together form an oxo group (═O),-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH,    C₁-C₄-alkyl and C₁-C₄-alkoxy,-   R¹¹ is hydrogen,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        —NH—C(O)—C₁-C₄-alkyl, —N(C₁-C₄-alkyl)-(—C(O)—C₁-C₄-alkyl),        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms;    -   phenyl, benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl, each of which is optionally substituted        by 1, 2 or 3 substituents independently selected from the group        consisting of halogen, cyano, —OH, oxo, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, C₃-C₆-cycloalkyl; and heterocyclyl-C₁-C₄-alkyl,        wherein the heterocyclyl substitutent is selected from the group        consisting of 4- to 10-membered heterocycloalkyl, 5-membered        heteroaryl and 6-membered heteroaryl, each of which is        optionally substituted by 1, 2 or 3 substituents independently        selected from the group consisting of halogen, cyano, —OH, oxo,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms;-   R¹⁵ is selected from the group consisting of hydrogen;    -   C₁-C₄-alkyl, phenyl-C₁-C₄-alkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, —OH, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms;-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹, Z², Z³, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, hydroxy,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, 4- to 6-membered        heterocyclyl, which is optionally substituted with 1 or 2        substituents selected from the group consisting of fluorine,        chlorine, bromine, methyl and cyano, —S—(C₁-C₄-alkyl),        —S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl), or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5- or 6-membered heterocycloalkyl, a 5-membered        heteroaryl, or a 6-membered heteroaryl, each of which may be        optionally substituted with one or two substituents selected        from the group consisting of methyl, fluorine and oxo, and    -   Z³, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-alkoxy-C(O)—, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, or    -   Z² and Z³ form, together with the carbon atoms that they are        connected to, a 5- or 6-membered saturated or partially        saturated heterocyclic ring, a 5-membered heteroaryl, or a        6-membered heteroaryl, each of which may be optionally        substituted with one or two substituents selected from the group        consisting of methyl, fluorine and oxo, and    -   Z¹, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q2)

-   -   in which:    -   Z⁶, Z⁷, Z⁸ and Z⁹ are independently selected from the group        consisting of hydrogen halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a pyrimidine ring of the formula (Q3)

-   -   in which:    -   Z¹⁰, Z¹¹ and Z¹² are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH—CO—C₁-C₄-alkyl, and monocyclic heterocycles selected from        the group of 4- to 7-membered heterocycloalkyl or 5-membered        heteroaryls having at least one nitrogen atom via which the        heteroaryl ring is connected to the pyridine ring, each of which        is optionally substituted with 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, —OH, oxo, thiono, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—(C₁-C₄-halogenoalkyl)        having 1 to 5 halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having        1 to 5 halogen atoms, —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5        halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, Z¹⁹ and Z²⁰ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        wherein when Y is O, S or N—R⁹, R¹⁰ is not —OH,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In accordance with a fourth embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0, 1 or 2,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X is selected from the group consisting of CR⁷R⁸, O, S, and N—R⁹,-   Y is CR⁷R⁸ or O,-   R¹ is hydrogen or C₁-C₄-alkyl,-   R² is selected from the group consisting of    -   hydrogen, halogen, —C(O)—N(C₁-C₄-alkyl)₂;    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl or        C₃-C₆-cycloalkenyl, each of which is optionally substituted by        1, 2, 3, 4 or 5 substituents independently selected from the        group consisting of halogen, —OH, cyano, C₁-C₄-alkoxy-C(O)— and        —C(O)—NH₂, C₁-C₄-alkoxy, —NH₂, —N(C₁-C₄-alkyl)₂,        —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl); and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, —OH, oxo, —COOH, C₁-C₄-alkoxy-C(O)—,        —C(O)—NH₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, hydroxy-C₁-C₄-alkyl-,        C₁-C₄-alkoxy-C₁-C₄-alkyl-, —NH₂, —N(C₁-C₄-alkyl)₂, and 4- to        10-membered heterocycloalkyl,-   R³ is hydrogen or C₁-C₄-alkyl,-   R⁴ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    —NH₂,-   R⁵ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy,-   R⁶ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁸ together form an oxo group (═O),-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH and    C₁-C₄-alkyl,-   R¹¹ is hydrogen,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—N(C₁-C₄-alkyl)₂, —NH—C(O)—C₁-C₄-alkyl, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₃-C₆-cycloalkyl, —NH₂, —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms and C₁-C₄-alkoxy;    -   phenyl and benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl each of which is optionally substituted by        1, 2 or 3 substituents independently selected from the group        consisting of halogen, —OH, oxo, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy and C₃-C₆-cycloalkyl; and 4- to        10-membered heterocycloalkyl,-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        —OH and —COOH; and    -   a 6-membered heteroaryl,-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, halogen, cyano, —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, —S—(C₁-C₄-alkyl) and a 4- to 6-membered heterocycloalkyl,        and    -   Z³ is selected from the group consisting of hydrogen, halogen,        C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, and —N(C₁-C₄-alkyl)₂, or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5-membered heterocycloalkyl or a 5-membered        heteroaryl, each of which may be optionally substituted with one        or two substituents selected from the group consisting of        methyl, fluorine and oxo,    -   Z³ and Z⁵ are hydrogen, and    -   Z⁴ is selected from the group consisting of hydrogen and        C₁-C₄-alkoxy-C(O)—, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —NH—CO—C₁-C₄-alkyl, and monocyclic        heterocycles selected from the group of 4- to 7-membered        heterocycloalkyl or 5-membered heteroaryls having at least one        nitrogen atom via which the heteroaryl ring is connected to the        pyridine ring, each of which is optionally substituted with 1, 2        or 3 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is halogen, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In accordance with a fifth embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is selected from the group consisting of

-   R¹ is hydrogen or methyl,-   R² is selected from the group consisting of    -   hydrogen, chlorine, iodine, —C(O)—N(CH₃)₂,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl,        cyclopentyl, cyclohexyl, ethenyl, propenyl, cyclopentenyl,        cyclohexenyl, each of which is optionally substituted by 1 or 2        substituents independently selected from the group consisting of        —OH, cyano, ethoxy-C(O)—, —C(O)—NH₂, methoxy, NH₂, N(CH₃)₂,        N(CH₃)(C(O)CH₃); and a monocyclic or a bicyclic heterocycle        selected from the group consisting of azetidine, oxetane,        pyrrolidine, tetrahydrofurane, pyrazolidine, imidazolidine,        1,2,4-triazolidine, piperidine, piperazine, tetrahydropyrane,        tetrahydropyridine, dihydro-2H-pyrane, 1,2-oxazolidine,        1,2-oxazine, morpholine, thiomorpholine,        3,4-dihydroisoquinoline, 2,3-dihydro-indole,        1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane,        6-oxa-3-azabicyclo[3.1.1]heptane,        8-oxa-3-azabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole,        1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine,        dihydropyridine, pyrimidine, tetrahydropyrimidine,        4-oxa-7-azaspiro[2.5]octane, each of which is optionally        substituted by 1, 2, 3 or 4 substituents independently selected        from the group consisting of fluorine, chlorine, cyano, —OH,        oxo, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—,        —C(O)—NH₂, methyl, methyl-C(O)—, difluoromethyl,        trifluoromethyl, hydroxymethyl-, methoxymethyl-, —NH₂, —NMe₂,        pyrrolidine,-   R³ is hydrogen or methyl,-   R⁴ is selected from the group consisting of hydrogen, fluorine,    chlorine, —OH, cyano, methyl, methoxy, trifluoromethyl,    trifluoromethoxy and NH₂,-   R⁵ is selected from the group consisting of hydrogen, fluorine,    chlorine, —OH, cyano, methyl, methoxy and trifluoromethyl,-   R⁶ is selected from the group consisting of hydrogen, fluorine,    chlorine, —OH, cyano, methyl and methoxy,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)-methyl), methoxy;    -   methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl,        cyclobutyl, benzyl, 1-phenylethyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of fluorine, —OH, —COOH,        methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,        —C(O)—NMe₂, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH₂,        NMe₂, S-methyl, S(O)-methyl, SO₂-methyl, and (EtO)₂P(═O)—;    -   heterocyclyl-methyl, heterocyclyl-ethyl, wherein the        heterocyclyl substituent is selected from the group consisting        of oxetane, tetrahydrofurane, tetrahydropyrane pyrrolidine,        morpholine, pyrazole, imidazole, 1, 2, 4-oxadiazole, pyridine,        each of which is optionally substituted by 1 substituent        independently selected from the group consisting of fluorine,        chlorine, —OH, oxo and methyl;    -   phenyl;    -   2,3-dihydro-1H-indene, and    -   a monocyclic or a bicyclic heterocycle selected from the group        of oxetane, thietane, pyrrolidine, morpholine, tetrahydropyrane,        pyridine and pyrazole, each of which is optionally substituted        by 1 or 2 substituents independently selected from the group        consisting of fluorine, chlorine, —OH, oxo, methyl;-   R¹⁴ is selected from the group consisting of    -   methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of        which is optionally substituted by 1 or 2 substituents        independently selected from the group consisting of fluorine,        —OH, methyl, methoxy and cyclopentyl; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of pyrrolidin and tetrahydropyran,-   R¹⁵ is selected from the group consisting of    -   methyl and ethyl, each of which is optionally substituted by 1        substituent independently selected from the group consisting of        —OH and —COOH; and pyridine,-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, methyl, trifluoromethyl and        methoxy,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, —OH, cyano, methyl, ethyl,        tert-butyl, —NHMe, —NMe₂, trifluoromethyl, methoxy,        trifluoromethoxy, —SMe and morpholinyl, and    -   Z³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy        and —NMe₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, fluorine, chlorine, cyano, methyl,        methoxy, ethoxy, isopropoxy, hydroxymethyl, NH₂, —NHMe —NMe₂,        —NH—C(O)-Me, morpholinyl, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is fluorine, chlorine, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²¹ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy and    -   Z²² is hydrogen, methyl, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy, or

-   Q is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In accordance with a sixth embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is selected from the group consisting of

-   R¹ is hydrogen or methyl,-   R² is selected from the group consisting of    -   chlorine, iodine, —C(O)—N(CH₃)₂,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl,        cyclopentyl, ethenyl, propenyl, each of which is optionally        substituted by 1 or 2 substituents independently selected from        the group consisting of —OH, cyano, ethoxy-C(O)—, —C(O)—NH₂,        methoxy, NH₂, N(CH₃)₂, N(CH₃)(C(O)CH₃); and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of azetidine, oxetane, pyrrolidine, tetrahydrofurane,        pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine,        piperazine, tetrahydropyrane, dihydro-2H-pyrane,        1,2-oxazolidine, morpholine, thiomorpholine,        3,4-dihydroisoquinoline, 2,3-dihydro-indole,        1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane,        6-oxa-3-azabicyclo[3.1.1]heptane,        8-oxa-3-azabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole,        1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine,        pyrimidine, tetrahydropyrimidine, each of which is optionally        substituted by 1, 2, 3 or 4 substituents independently selected        from the group consisting of fluorine, —OH, oxo, —COOH,        methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,        methyl, methyl-C(O)—, difluoromethyl, trifluoromethyl,        hydroxymethyl-, methoxymethyl-, —NH₂, —NMe₂, pyrrolidine,-   R³ is hydrogen or methyl,-   R⁴ is selected from the group consisting of hydrogen, chlorine,    fluorine, methyl, methoxy and trifluoromethyl,-   R⁵ is selected from the group consisting of hydrogen, chlorine,    fluorine, —OH, cyano, methyl, trifluoromethoxy and NH₂,-   R⁶ is selected from the group consisting of hydrogen, fluorine,    chlorine, —OH, cyano, methyl and methoxy,-   R¹² and R¹³ are independently selected from the group consisting of    hydrogen, —NH(—C(O)-methyl), methoxy;    -   methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl,        cyclobutyl, benzyl, 1-phenylethyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of fluorine, —OH, —COOH,        methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,        —C(O)—NMe₂, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH₂,        —NMe₂, SO₂-methyl and (EtO)₂P(═O)—;    -   heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocycyl        substituent is selected from the group consisting of oxetane,        tetrahydrofurane, tetrahydropyrane, pyrrolidine, pyrazole,        imidazole, 1, 2, 4-oxadiazole, morpholine, pyridine, each of        which is optionally substituted by 1 substituent independently        selected from the group consisting of oxo and methyl;    -   phenyl;    -   2,3-dihydro-1H-indene, and    -   a monocyclic or a bicyclic heterocycle selected from the group        of oxetane, morpholine, tetrahydropyrane, pyridine and pyrazole;-   R¹⁴ is selected from the group consisting of    -   methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of        which is optionally substituted by 1 or 2 substituents        independently selected from the group consisting of fluorine,        —OH, methyl, methoxy and cyclopentyl; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of pyrrolidin and tetrahydropyran,-   R¹⁵ is selected from the group consisting of    -   methyl and ethyl, each of which is optionally substituted by 1        substituent independently selected from the group consisting of        —OH and —COOH; and pyridine,-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, methyl, methoxy and        trifluoromethyl,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, —OH, cyano, methyl, ethyl,        tert-butyl, —NHMe, —NMe₂, trifluoromethyl, methoxy,        trifluoromethoxy, —SMe and morpholinyl, and    -   Z³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy        and —NMe₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹⁴ and Z¹⁵ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, cyano, methyl, methoxy, ethoxy,        isopropoxy, hydroxymethyl, NH₂, morpholinyl and    -   Z¹³ and Z¹⁶ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, methyl, methoxy, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is fluorine, or

-   Q is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In accordance with a seventh embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is selected from the group consisting of

-   R¹ is hydrogen or methyl,-   R² is selected from the group consisting of hydrogen,    (1S)-2,3-dihydro-1H-inden-1-ylamino, (2,3-difluorobenzyl)oxy,    (2-acetamidoethyl)amino, (2-amino-2-oxoethyl)amino,    (2-aminoethyl)amino, (2-carboxyethyl)sulfanyl,    (2-ethoxy-2-oxoethyl)(methyl)amino, (2-hydroxyethyl)(methyl)amino,    (2-hydroxyethyl)amino, hydroxymethyl, methoxymethyl, 2-hydroxyethyl,    (2-hydroxyethyl)oxy, (2-hydroxyethyl)sulfanyl,    (2-methoxy-2-oxoethyl)amino, (3-methoxy-3-oxopropyl)-methylamino,    (2-methoxyethyl)(methyl)amino, (2-methoxyethyl)amino,    (2-methoxyethyl)oxy, (2R)-2-(hydroxymethyl)pyrrolidin-1-yl,    (2R)-2-(methoxycarbonyl)pyrrolidin-1-yl,    (2R)-2-(methoxymethyl)pyrrolidin-1-yl,    (2R)-2-(tert-butoxycarbonyl)pyrrolidin-1-yl,    (2R)-2-carboxylatopyrrolidin-1-yl, (2R)-2-carboxypyrrolidin-1-yl,    (2R,6S)-2,6-dimethylmorpholin-4-yl,    2-(trifluoromethyl)morpholin-4-yl, (2rac)-2-carboxpyrrolidin-1-yl,    (2S)-2-(ethoxycarbonyl) pyrrolidin-1-yl,    (2S)-2-(hydroxymethyl)pyrrolidin-1-yl,    (2S)-2-(methoxycarbonyhpyrrolidin-1-yl,    (2S)-2-(methoxymethyl)pyrrolidin-1-yl,    (2S)-2-(tert-butoxycarbonyhpyrrolidin-1-yl,    (2S)-2-carbamoylpyrrolidin-1-yl, (2S)-2-carboxypyrrolidin-1-yl,    (2S)-2-methyl-2,3-dihydro-1H-indol-1-yl,    (2S)-2-methylmorpholin-4-yl,    (2-tert-butoxy-2-oxoethyl)(methyl)amino,    (2-tert-butoxy-2-oxoethyl)amino, 2,2-difluoroethyl(methyl)amino,    (3,3,3-trifluoropropyl)amino, (3,3-dimethylbutyl)oxy,    (3-amino-3-oxopropyl)(methyl)amino, (3-amino-3-oxopropyl)amino,    (3-fluorobenzyl)oxy, (3-methoxy-3-methylbutyl)oxy,    (3-methoxybenzyl)oxy, (3R)-3-(hydroxymethyl)pyrrolidin-1-yl,    (3R)-3-(methoxycarbonyl)pyrrolidin-1-yl,    (3R)-3-aminopyrrolidin-1-yl, (3R)-3-carboxypyrrolidin-1-yl,    (3R)-3-hydroxpyrrolidin-1-yl, (3R)-pyrrolidin-3-yloxy,    (3rac,4rac)-3-amino-4-fluoropyrrolidin-1-yl,    (3S)-3-(dimethylamino)pyrrolidin-1-yl,    (3S)-3-(hydroxymethyl)pyrrolidin-1-yl,    (3S)-3-(methoxycarbonyhpyrrolidin-1-yl,    (3S)-3-hydroxypyrrolidin-1-yl, (carboxylatomethyl)amino,    (carboxymethyl)(methyl)amino, (carboxyethyl)amino,    (cyclopentylmethyl)oxy, (cyclopropylmethyl)(methyl)amino,    (pyridin-2-ylmethyl)amino, (rac)-3-hydroxpyrrolidin-1-yl,    [(1R,3S)-3-amino-2,2-dimethylcyclopropyl]amino,    [(2R)-1-hydroxybutan-2-yl]amino,    [(2S)-1-amino-1-oxopropan-2-yl]amino,    [(5-methyl-1,2,4-oxadiazol-3-yl)methyl]amino,    [(diethoxyphosphoryl)methyl](methyl)amino,    [2-(1H-pyrazol-1-yl)ethyl]amino, 2-(1H-imidazol-1-yl)ethylamino,    2-(1H-imidazol-1-yl)ethyl-methylamino,    [2-(cyclopropylamino)ethyl]amino, [2-(dimethylamino)ethyl]amino,    [2-(pyrrolidin-1-yl)ethyl]amino,    [3-(dimethylamino)-3-oxopropyl]amino, 1,1-dioxidothiomorpholin-4-yl,    1,2-oxazolidin-2-yl, 1,3-dihydro-2H-isoindol-2-yl,    1-cyano-2-ethoxy-2-oxoethyl, 1H-1,2,3-triazol-1-yl,    1H-imidazol-1-yl, 1H-pyrazol-1-yl, 1H-pyrazol-4-yl,    1H-pyrazol-4-ylamino, 2,2-dimethylmorpholin-4-yl,    2,2-dimethylpyrrolidin-1-yl,    2,4-dimethyl-3,5-dioxo-1,2,4-triazolidin-1-yl, 2-acetylhydrazino,    2-amino-2-oxoethyl, 2H-1,2,3-triazol-2-yl, 1H-tetrazol-5-yl,    3-(pyrrolidin-1-yl)azetidin-1-yl, 3,3-difluoroazetidin-1-yl,    3,3-difluoropyrrolidin-1-yl, 3,4-dihydroisoquinolin-2(1H)-yl,    3,9-dioxa-7-azabicyclo[3.3.1]non-7-yl, 3-fluoroazetidin-1-yl,    3-hydroxyazetidin-1-yl, 3-methylazetidin-1-yl,    3-oxopyrazolidin-1-yl, 1-(difluoromethyl)-1H-pyrazol-4-yl,    4-(trifluoromethyl)-1H-pyrazol-1-yl, 1-methyl-piperidin-4-yl,    4-fluoropiperidin-1-yl, 4,4-difluoropiperidin-1-yl,    4-acetylpiperazin-1-yl, 4-oxoimidazolidin-1-yl,    6-oxa-3-azabicyclo[3.1.1]hept-3-yl,    8-oxa-3-azabicyclo[3.2.1]oct-3-yl, amino, anilino, azetidin-1-yl,    benzyl(methyl)amino, bis(2-methoxyethyl)amino, chlorine, iodine,    cyanomethyl, cyclobutyl(methyl)amino, cyclopentyloxy, cyclopropyl,    cyclobutyl, cyclopentyl, cyclopropyl(ethyl)amino,    cyclopropyl(methyl)amino, cyclopropylamino, diethylamino,    dimethylamino, dimethylaminocarbonyl, aminomethyl, 2-aminoethyl,    (dimethylamino)methyl, 2-(dimethylamino)ethyl,    [acetyl(methyl)amino]methyl, ethenyl, ethyl,    ethyl(2-methoxyethyl)amino, ethylamino, ethyloxy, ethylsulfanyl,    ethylsulfinyl, ethylsulfonyl, ethyl(methyl)amino,    isobutyl(methyl)amino, isopropyl(methyl)amino, isopropyl,    isopropyloxy, methoxy(methyl)amino, methoxyamino, methyl,    methyl(2-methylsulfonylethyl)amino, methyl-oxolan-3-yl]methyl]amino,    methyl(oxan-4-ylmethyl)amino, methyl(1-phenylethyl)amino,    methyl(2,2,2-trifluoroethyl)amino, oxetan-3-ylmethylamino,    methyl(oxetan-3-yl)amino, methyl(phenyl)amino,    methyl[2-(2-oxopyrrolidin-1-yl)ethyl]amino,    methyl[2-(morpholin-4-yl)ethyl]amino, methylamino, methyloxy,    methylsulfanyl, morpholin-4-yl, morpholin-4-ylamino, nitrilomethyl,    prop-1-en-2-yl, propyl, propylamino, pyridin-4-yl,    pyridin-2-ylsulfanyl, pyridin-4-ylamino, pyrrolidin-1-yl,    pyrrolidin-3-yl, oxetan-3-yl, tetrahydrofuran-3-yl,    3,6-dihydro-2H-pyran-4-yl, tetrahydropyran-4-yl,    tetrahydro-2H-pyran-4-ylamino, tetrahydro-2H-pyran-4-yloxy,    2-aminopyrimidin-5-yl,    1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl,    3-fluoro-2-oxo-1,2-dihydropyridin-5-yl,    2-oxo-1,2-dihydropyridin-5-yl, 3-thienyl and thiomorpholin-4-yl,-   R³ is hydrogen or methyl,-   R⁴ is selected from the group consisting of hydrogen, chlorine,    fluorine, —OH, cyano, methyl, methoxy, trifluoromethyl,    trifluoromethoxy and NH₂,-   R⁵ is selected from the group consisting of hydrogen, chlorine,    fluorine, —OH, cyano, methyl, methoxy and trifluoromethyl,-   R⁶ is selected from the group consisting of hydrogen, fluorine,    chlorine, —OH, cyano, methyl and methoxy,-   Q is selected from the group consisting of phenyl,    1,3-benzothiazol-4-yl, 1,3-benzothiazol-7-yl, 1,3-benzoxazol-7-yl,    1H-indol-4-yl, 1-methyl-1H-benzimidazol-6-yl,    2,5-bis(trifluoromethyl)phenyl, 2,3,4-trifluorophenyl,    2,3,5-trichlorophenyl, 2,3,5-trifluorophenyl, 2,3,6-trifluorophenyl,    2,3-dichlorophenyl, 2,3-dichloro-5-cyanophenyl,    2,3-dichloro-5-hydroxyphenyl, 2,3-dihydro-1-benzofuran-7-yl,    2,3-difluorophenyl, 2,4,5-trifluorophenyl,    2,4,6-trifluoro-3-methoxyphenyl, 2,4-difluoro-3-hydroxyphenyl,    2,4-difluoro-3-methoxyphenyl, 2,5-dichlorophenyl,    2-chloro-5-cyanophenyl, 2-chloro-5-methylphenyl,    2,5-difluoro-4-methoxyphenyl, 2,6-difluorophenyl,    2-chloro-6-methylpyridin-4-yl, 3-methylpyridin-4-yl,    2,6-dimethylpyridin-4-yl, 2-chloro-3-fluorophenyl,    2-chloro-4-(dimethylamino)phenyl, 2-chloro-4-fluorophenyl,    2-chloro-5-fluorophenyl, 2-chloro-6-fluorophenyl, 2-chlorophenyl,    2-chloropyridin-4-yl, 3-chloropyridin-4-yl,    2,3-dichloropyridin-4-yl, 2,5-dichloropyridin-4-yl,    2,6-dichloropyridin-4-yl, 3,5-dichloropyridin-4-yl,    2,6-difluoropyridin-4-yl, 3,5-difluoropyridin-4-yl,    2-chloro-3-fluoropyridin-4-yl, 2-cyanopyridin-4-yl,    3-chloro-2-methoxypyridin-4-yl, 5-chloro-2-methoxypyridin-4-yl,    5-fluoro-2-methoxypyridin-4-yl, 5-fluoro-2-isopropyloxypyridin-4-yl,    2,3-dimethoxypyridin-4-yl, 2,6-dimethoxypyridin-4-yl,    2-fluoro-5-methylphenyl, 3-fluoro-5-methylphenyl,    2-fluoro-3-(trifluoromethoxy)phenyl,    2-fluoro-3-(trifluoromethyl)phenyl,    5-fluoro-2-(trifluoromethyl)phenyl, 3-cyano-5-methylphenyl,    2-fluoropyridin-4-yl, 2-ethoxy-5-fluoropyridin-4-yl,    2-(hydroxymethyl)pyridin-4-yl, 2-methylypyridin-4-yl,    2-methoxypyridin-4-yl, 3-methoxypyridin-4-yl, 2-aminopyridin-4-yl,    2-morpholin-4-ylpyridin-4-yl, 3-(dimethylamino)-2,4-difluorophenyl,    3-(dimethylamino)phenyl, 3-(methylamino)phenyl,    3-(trifluoromethyly)phenyl, 3-(trifluoromethoxy)phenyl,    3,4,5-trifluorophenyl, 3,4-dichloro-5-(dimethylamino)phenyl,    3,4-dichlorophenyl, 3,4-difluoro-2-methoxyphenyl,    3,4-difluorophenyl, 3,5-dichloro-4-(dimethylamino)phenyl,    3,5-dichloro-4-fluorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl,    4-(difluoromethoxy)-3,5-difluorophenyl, 2,5-dimethylphenyl,    3,5-dimethylphenyl, 3-tert-butyl-5-methylphenyl,    5-tert-butyl-2-chloro-3-methylphenyl,    3-chloro-2-fluoro-5-methylphenyl, 3-chloro-2-fluorophenyl,    3-chloro-2-methylphenyl, 3-chloro-4-(dimethylamino)-5-fluorophenyl,    3-chloro-4-(dimethylamino)phenyl, 3-chloro-4-fluorophenyl,    3-chloro-4-methylphenyl, 3-chloro-5-(dimethylamino)phenyl,    3-chloro-5-(methylsulfanyl)phenyl,    3-chloro-5-(morpholin-4-yl)phenyl,    2-chloro-3-(trifluoromethyl)phenyl,    2-methyl-5-(trifluoromethyl)phenyl,    3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-ethylphenyl,    3-chloro-5-fluorophenyl, 3-chloro-5-methoxyphenyl,    3-chloro-5-methylphenyl, 3-chlorophenyl, 3-fluoro-2-methylphenyl,    3-fluoro-4-methoxyphenyl, 3-fluoro-5-methylphenyl,    3-fluoropyridin-2-yl, 3-fluoropyridin-4-yl,    4-chloro-3-(dimethylamino)phenyl, 4-fluoro-3-methoxyphenyl,    5-(methoxycarbonyl)-1,3-benzoxazol-7-yl,    5-chloro-2,4-difluorophenyl, 5-chloro-2-fluoro-3-methylphenyl,    5-chloro-2-fluoro-4-methylphenyl, 5-chloro-2-fluorophenyl,    5-chloro-2-methoxyphenyl, 5-fluoro-2-methylphenyl,    5-fluoro-2-methoxyphenyl, 5-chloro-1H-imidazol-2-yl,    3,5-diethylphenyl, 2-chloro-3,5-diethylphenyl, 3-chloro-2-thienyl,    4-chloro-2-thienyl, 5-chloro-2-thienyl, 2,5-dichloro-3-thienyl,    5-fluoro-2-thienyl, 5-cyano-2-thienyl, 5-cyano-4-methyl-2-thienyl,    5-methyl-2-thienyl, 2,5-dimethyl-3-thienyl,    5-(trifluoromethyl)-2-thienyl and 2-methyl-1,3-thiazol-5-yl, and    stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts    thereof, and mixtures of same.

In accordance with an eight embodiment of the first aspect, the presentinvention covers compounds of general formula (I), supra, in which:

-   A is A3 or A4

-   o is 0 or 1,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X is selected from the group consisting of CR⁷R⁸, O, S, and N—R⁹,-   Y is CR⁷R⁸ or O,-   R¹ is hydrogen or C₁-C₄-alkyl,-   R² is selected from the group consisting of hydrogen, halogen,    —C(O)—N(C₁-C₄-alkyl)₂;    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl or        C₃-C₆-cycloalkenyl, each of which is optionally substituted by        1, 2, 3, 4 or 5 substituents independently selected from the        group consisting of halogen, —OH, cyano, C₁-C₄-alkoxy-C(O)— and        —C(O)—NH₂C₁-C₄-alkoxy, —NH₂, —N(C₁-C₄-alkyl)₂,        —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, —OH, oxo, —COOH, C₁-C₄-alkoxy-C(O)—,        —C(O)—NH₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, hydroxy-C₁-C₄-alkyl-,        C₁-C₄-alkoxy-C₁-C₄-alkyl-, —NH₂, —N(C₁-C₄-alkyl)₂, and 4- to        10-membered heterocycloalkyl,-   R³ is hydrogen or C₁-C₄-alkyl,-   R⁴ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, NH₂,-   R⁵ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R⁶ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁸ together form an oxo group (═O),-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH and    C₁-C₄-alkyl,-   R¹¹ is hydrogen,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—N(C₁-C₄-alkyl)₂, —NH—C(O)—C₁-C₄-alkyl, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₃-C₆-cycloalkyl, —NH₂, —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms and C₁-C₄-alkoxy;    -   phenyl and benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl each of which is optionally substituted by        1, 2 or 3 substituents independently selected from the group        consisting of halogen, —OH, oxo, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy and C₃-C₆-cycloalkyl; and 4- to        10-membered heterocycloalkyl,-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        —OH and —COOH; and    -   a 6-membered heteroaryl,-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, halogen, cyano, —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, —S—(C₁-C₄-alkyl) and a 4- to 6-membered heterocycloalkyl,        and    -   Z³ is selected from the group consisting of hydrogen, halogen,        C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms and —N(C₁-C₄-alkyl)₂, or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5-membered heterocycloalkyl or a 5-membered        heteroaryl, each of which may be optionally substituted with one        or two substituents selected from the group consisting of        methyl, fluorine and oxo,    -   Z³ and Z⁵ are hydrogen, and    -   Z⁴ is selected from the group consisting of hydrogen and        C₁-C₄-alkoxy-C(O)—, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —NH—CO—C₁-C₄-alkyl, and monocyclic        heterocycles selected from the group of 4- to 7-membered        heterocycloalkyl or 5-membered heteroaryls having at least one        nitrogen atom via which the heteroaryl ring is connected to the        pyridine ring, each of which is optionally substituted with 1, 2        or 3 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is halogen, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

Further embodiments of the first aspect of the present invention:

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0, 1 or 2,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy, cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms,-   R_(p) is hydrogen,-   X, Y are independently selected from the group consisting of CR⁷R⁸,    O, S, and N—R⁹, wherein at least one of X and Y is CR⁷R⁸,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH,    C₁-C₄-alkyl and C₁-C₄-alkoxy, and-   R¹¹ is hydrogen,-   wherein when Y is O, S or N—R⁹, R¹⁰ is not —OH,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0, 1 or 2,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy, cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X, Y are independently selected from the group consisting of CR⁷R⁸,    O, S, and N—R⁹, wherein at least one of X and Y is CR⁷R⁸,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁸ together form an oxo group (═O),-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH,    C₁-C₄-alkyl and C₁-C₄-alkoxy, and-   R¹¹ is hydrogen,    wherein when Y is O, S or N—R⁹, R¹⁰ is not —OH,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0, 1 or 2,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy, cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen    atoms,-   R_(p) is hydrogen,-   X, Y are independently selected from the group consisting of CR⁷R⁸,    O, and S,    -   wherein at least one of X and Y is CR⁷R⁸,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁸ together form an oxo group (═O),-   R¹⁰ is selected from the group consisting of hydrogen, —OH,    C₁-C₄-alkyl and C₁-C₄-alkoxy, and-   R¹¹ is hydrogen,    wherein when Y is O, S or N—R⁹, R¹⁰ is not —OH,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0 or 1,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy,-   R_(p) is hydrogen,-   X is selected from the group consisting of CR⁷R⁸, O, S, and N—R⁹,-   Y is CR⁷R⁸,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH and    C₁-C₄-alkyl, and-   R¹¹ is hydrogen,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0 or 1,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy,-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl,-   X is selected from the group consisting of CR⁷R⁸, O, S, and N—R⁹,-   Y is CR⁷R⁸ or O,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁸ together form an oxo group (═O),-   R⁹ is C₁-C₄-alkyl,-   R¹⁰ is selected from the group consisting of hydrogen, —OH and    C₁-C₄-alkyl, and-   R¹¹ is hydrogen,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is A1 or A2,

-   o is 0 or 1,-   R is selected from the group consisting of halogen, C₁-C₄-alkyl and    C₁-C₄-alkoxy,-   R_(p) is hydrogen,-   X is selected from the group consisting of CR⁷R⁸, O and S,-   Y is CR⁷R⁸ or O,-   R⁷ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   R⁸ is selected from the group consisting of hydrogen and    C₁-C₄-alkyl,-   or R⁷ and R⁸ together form an oxo group (═O),-   R¹⁰ is selected from the group consisting of hydrogen, —OH and    C₁-C₄-alkyl, and-   R¹¹ is hydrogen,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   A is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R² is selected from the group consisting of    -   hydrogen, halogen, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,        C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of        which is optionally substituted by 1, 2, 3, 4 or 5 substituents        independently selected from the group consisting of halogen,        —OH, cyano, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms; and a monocyclic or a bicyclic heterocycle        selected from the group consisting of 4- to 10-membered        heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl        and 6-membered heteroaryl, each of which is optionally        substituted by 1, 2, 3 or 4 substituents independently selected        from the group consisting of halogen, cyano, —OH, oxo, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, and        4- to 10-membered heterocycloalkyl,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        —NH—C(O)—C₁-C₄-alkyl, —N(C₁-C₄-alkyl)-(—C(O)—C₁-C₄-alkyl),        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms;    -   phenyl, benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl, each of which is optionally substituted        by 1, 2 or 3 substituents independently selected from the group        consisting of halogen, cyano, —OH, oxo, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, C₃-C₆-cycloalkyl; and    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substitutent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms;-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, phenyl-C₁-C₄-alkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, —OH, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms;

heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms;

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R² is selected from the group consisting of    -   hydrogen, halogen, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,        C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of        which is optionally substituted by 1, 2, 3, 4 or 5 substituents        independently selected from the group consisting of halogen,        —OH, cyano, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —NH(C(O)—C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms and —SO₂—C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, cyano, —OH, oxo, —COOH,        C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),        —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, and        4- to 10-membered heterocycloalkyl,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,        —NH—C(O)—C₁-C₄-alkyl, —N(C₁-C₄-alkyl)-(—C(O)—C₁-C₄-alkyl),        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms;    -   phenyl, benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl, each of which is optionally substituted        by 1, 2 or 3 substituents independently selected from the group        consisting of halogen, cyano, —OH, oxo, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms, C₃-C₆-cycloalkyl; and heterocyclyl-C₁-C₄-alkyl,        wherein the heterocyclyl substitutent is selected from the group        consisting of 4- to 10-membered heterocycloalkyl, 5-membered        heteroaryl and 6-membered heteroaryl, each of which is        optionally substituted by 1, 2 or 3 substituents independently        selected from the group consisting of halogen, cyano, —OH, oxo,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms;-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, phenyl-C₁-C₄-alkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, —OH, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5        halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms;        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R² is selected from the group consisting of    -   hydrogen, halogen,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl or        C₃-C₆-cycloalkenyl, each of which is optionally substituted by        1, 2, 3, 4 or 5 substituents independently selected from the        group consisting of halogen, cyano, C₁-C₄-alkoxy-C(O)— and        —C(O)—NH₂; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, —OH, oxo, —COOH, C₁-C₄-alkoxy-C(O)—,        —C(O)—NH₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, hydroxy-C₁-C₄-alkyl-,        C₁-C₄-alkoxy-C₁-C₄-alkyl-, —NH₂, —N(C₁-C₄-alkyl)₂, and 4- to        10-membered heterocycloalkyl,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—N(C₁-C₄-alkyl)₂, —NH—C(O)—C₁-C₄-alkyl, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₃-C₆-cycloalkyl, —NH₂, —N(C₁-C₄-alkyl)₂, alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, and (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms and C₁-C₄-alkoxy;    -   phenyl and benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl each of which is optionally substituted by        1, 2 or 3 substituents independently selected from the group        consisting of halogen, —OH, oxo, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy and C₃-C₆-cycloalkyl; and 4- to        10-membered heterocycloalkyl,-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        —OH and —COOH; and a 6-membered heteroaryl,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R² is selected from the group consisting of    -   hydrogen, halogen, —C(O)—N(C₁-C₄-alkyl)₂    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl or        C₃-C₆-cycloalkenyl, each of which is optionally substituted by        1, 2, 3, 4 or 5 substituents independently selected from the        group consisting of halogen, —OH, cyano, C₁-C₄-alkoxy-C(O)— and        —C(O)—NH₂, C₁-C₄-alkoxy, —NH₂, —N(C₁-C₄-alkyl)₂,        —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl); and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of 4- to 10-membered heterocycloalkyl,        heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2, 3        or 4 substituents independently selected from the group        consisting of halogen, —OH, oxo, —COOH, C₁-C₄-alkoxy-C(O)—,        —C(O)—NH₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, hydroxy-C₁-C₄-alkyl-,        C₁-C₄-alkoxy-C₁-C₄-alkyl-, —NH₂, —N(C₁-C₄-alkyl)₂, and 4- to        10-membered heterocycloalkyl,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy;    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,        —C(O)—N(C₁-C₄-alkyl)₂, —NH—C(O)—C₁-C₄-alkyl, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₃-C₆-cycloalkyl, —NH₂, —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, and        (C₁-C₄-alkoxy)₂P(═O)—;    -   heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent        is selected from the group consisting of 4- to 10-membered        heterocycloalkyl, 5-membered heteroaryl and 6-membered        heteroaryl, each of which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        halogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms and C₁-C₄-alkoxy;    -   phenyl and benzo-C₅-C₆-cycloalkyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms; and    -   a monocyclic or a bicyclic heterocycle selected from the group        of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and        6-membered heteroaryl each of which is optionally substituted by        1, 2 or 3 substituents independently selected from the group        consisting of halogen, —OH, oxo, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,-   R¹⁴ is selected from the group consisting of    -   C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which        is optionally substituted by 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy and C₃-C₆-cycloalkyl; and    -   4- to 10-membered heterocycloalkyl,-   R¹⁵ is selected from the group consisting of    -   hydrogen;    -   C₁-C₄-alkyl, which is optionally substituted by 1, 2 or 3        substituents independently selected from the group consisting of        —OH and —COOH; and    -   a 6-membered heteroaryl,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R² is selected from the group consisting of    -   hydrogen, chlorine,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclohexyl,        propenyl, cyclopentenyl, cyclohexenyl, each of which is        optionally substituted by 1 or 2 substituents independently        selected from the group consisting of cyano, ethoxy-C(O)—, and        —C(O)—NH₂; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of azetidine, pyrrolidine, pyrazolidine,        imidazolidine, 1,2,4-triazolidine, piperidine, piperazine,        tetrahydropyridine, dihydro-2H-pyrane, 1,2-oxazolidine,        1,2-oxazine, morpholine, thiomorpholine,        3,4-dihydroisoquinoline, 2,3-dihydro-indole,        1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane,        6-oxa-3-azabicyclo[3.1.1]heptane,        8-oxa-3-azabicyclo[3.2.1]octane, imidazole, pyrazole,        1,2,4-triazole, 1,2,3-triazole, 4-oxa-7-azaspiro[2.5]octane,        each of which is optionally substituted by 1, 2, 3 or 4        substituents independently selected from the group consisting of        fluorine, chlorine, cyano —OH, oxo, —COOH, methoxy-C(O)—,        ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂, methyl,        methyl-C(O)—, trifluoromethyl, hydroxymethyl-, methoxymethyl-,        —NH₂, —NMe₂, pyrrolidine,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)-methyl), methoxy;    -   methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl,        cyclobutyl, benzyl, 1-phenylethyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of fluorine, —OH, —COOH,        methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,        —C(O)—NMe₂, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH₂,        NMe₂, S-methyl, S(O)-methyl, SO₂-methyl, and (EtO)₂P(═O)—;    -   heterocyclyl-methyl, heterocyclyl-ethyl, wherein the        heterocyclyl substituent is selected from the group consisting        of pyrrolidine, morpholine, pyrazole, 1, 2, 4-oxadiazole,        pyridine, each of which is optionally substituted by 1        substituent independently selected from the group consisting of        fluorine, chlorine, —OH, oxo and methyl;    -   phenyl;    -   2,3-dihydro-1H-indene, and    -   a monocyclic or a bicyclic heterocycle selected from the group        of oxetane, thietane, pyrrolidine, morpholine, tetrahydropyrane,        pyridine and pyrazole, each of which is optionally substituted        by 1 or 2 substituents independently selected from the group        consisting of fluorine, chlorine, —OH, oxo, methyl;-   R¹⁴ is selected from the group consisting of    -   methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of        which is optionally substituted by 1 or 2 substituents        independently selected from the group consisting of fluorine,        —OH, methyl, methoxy and cyclopentyl; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of pyrrolidin and tetrahydropyran,-   R¹⁵ is selected from the group consisting of    -   methyl and ethyl, each of which is optionally substituted by 1        substituent independently selected from the group consisting of        —OH and —COOH; and pyridine,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R² is selected from the group consisting of    -   hydrogen, chlorine, iodine, —C(O)—N(CH₃)₂,    -   —NR¹²R¹³;    -   —OR¹⁴;    -   —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵;    -   methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl,        cyclopentyl, cyclohexyl, ethenyl, propenyl, cyclopentenyl,        cyclohexenyl, each of which is optionally substituted by 1 or 2        substituents independently selected from the group consisting of        —OH, cyano, ethoxy-C(O)—, —C(O)—NH₂, methoxy, NH₂, N(CH₃)₂,        N(CH₃)(C(O)CH₃); and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of azetidine, oxetane pyrrolidine, tetrahydrofurane,        pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine,        piperazine, tetrahydropyridine, dihydro-2H-pyrane,        1,2-oxazolidine, 1,2-oxazine, morpholine, thiomorpholine,        3,4-dihydroisoquinoline, 2,3-dihydro-indole,        1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane,        6-oxa-3-azabicyclo[3.1.1]heptane,        8-oxa-3-azabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole,        1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine,        dihydropyridine pyrimidine, tetrahydropyrimidine,        4-oxa-7-azaspiro[2.5]octane, each of which is optionally        substituted by 1, 2, 3 or 4 substituents independently selected        from the group consisting of fluorine, chlorine, cyano —OH, oxo,        —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—,        —C(O)—NH₂, methyl, methyl-C(O)—, difluoromethyl,        trifluoromethyl, hydroxymethyl-, methoxymethyl-, —NH₂, —NMe₂,        pyrrolidine,-   R¹² and R¹³ are independently selected from the group consisting of    -   hydrogen, —NH(—C(O)-methyl), methoxy;    -   methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl,        cyclobutyl, benzyl, 1-phenylethyl, each of which is optionally        substituted by 1, 2 or 3 substituents independently selected        from the group consisting of fluorine, —OH, —COOH,        methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,        —C(O)—NMe₂, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH₂,        NMe₂, S-methyl, S(O)-methyl, 50₂-methyl, and (EtO)₂P(═O)—;    -   heterocyclyl-methyl, heterocyclyl-ethyl, wherein the        heterocyclyl substituent is selected from the group consisting        of oxetane, tetrahydrofurane, tetrahydropyrane pyrrolidine,        morpholine, pyrazole, imidazole, 1, 2, 4-oxadiazole, pyridine,        each of which is optionally substituted by 1 substituent        independently selected from the group consisting of fluorine,        chlorine, —OH, oxo and methyl;    -   phenyl;    -   2,3-dihydro-1H-indene, and a monocyclic or a bicyclic        heterocycle selected from the group of oxetane, thietane,        pyrrolidine, morpholine, tetrahydropyrane, pyridine and        pyrazole, each of which is optionally substituted by 1 or 2        substituents independently selected from the group consisting of        fluorine, chlorine, —OH, oxo, methyl;-   R¹⁴ is selected from the group consisting of    -   methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of        which is optionally substituted by 1 or 2 substituents        independently selected from the group consisting of fluorine,        —OH, methyl, methoxy and cyclopentyl; and    -   a monocyclic or a bicyclic heterocycle selected from the group        consisting of pyrrolidin and tetrahydropyran,-   R¹⁵ is selected from the group consisting of    -   methyl and ethyl, each of which is optionally substituted by 1        substituent independently selected from the group consisting of        —OH and —COOH; and pyridine,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R_(p) is hydrogen or C₁-C₄-alkyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R_(p) is hydrogen or methyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R³ is hydrogen or C₁-C₄-alkyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R³ is hydrogen or methyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁴ is selected from the group consisting of hydrogen, halogen,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁴ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, NH₂,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁴ is selected from the group consisting of hydrogen, chlorine,    fluorine, cyano, methyl, methoxy and trifluoromethyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁴ is selected from the group consisting of hydrogen, chlorine,    fluorine, —OH, cyano, methyl, methoxy, trifluoromethyl,    trifluoromethoxy and NH₂,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁵ is selected from the group consisting of hydrogen, halogen,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁵ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁵ is selected from the group consisting of hydrogen, chlorine,    fluorine and methyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁵ is selected from the group consisting of hydrogen, chlorine,    fluorine, —OH, cyano, methyl, methoxy and trifluoromethyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁶ is selected from the group consisting of hydrogen, halogen,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁶ is selected from the group consisting of hydrogen, halogen, —OH,    cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,    C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁶ is selected from the group consisting of hydrogen, fluorine,    chlorine and methyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   R⁶ is selected from the group consisting of hydrogen, fluorine,    chlorine, —OH, cyano, methyl and methoxy,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹, Z², Z³, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, hydroxy,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, 4- to 6-membered        heterocyclyl, which is optionally substituted with 1 or 2        substituents selected from the group consisting of fluorine,        chlorine, bromine, methyl and cyano, —S—(C₁-C₄-alkyl),        —S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl), or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5- or 6-membered heterocycloalkyl, a 5-membered        heteroaryl, or a 6-membered heteroaryl, each of which may be        optionally substituted with one or two substituents selected        from the group consisting of methyl, fluorine and oxo, and    -   Z³, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-alkoxy-C(O)—, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, or    -   Z² and Z³ form, together with the carbon atoms that they are        connected to, a 5- or 6-membered saturated or partially        saturated heterocyclic ring, a 5-membered heteroaryl, or a        6-membered heteroaryl, each of which may be optionally        substituted with one or two substituents selected from the group        consisting of methyl, fluorine and oxo, and    -   Z¹, Z⁴, and Z⁵ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q2)

-   -   in which:    -   Z⁶, Z⁷, Z⁹ and Z⁹ are independently selected from the group        consisting of hydrogen halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a pyrimidine ring of the formula (Q3)

-   -   in which:    -   Z¹⁰, Z¹¹ and Z¹² are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —NH—CO—C₁-C₄-alkyl, and monocyclic heterocycles selected from        the group of 4- to 7-membered heterocycloalkyl or 5-membered        heteroaryls having at least one nitrogen atom via which the        heteroaryl ring is connected to the pyridine ring, each of which        is optionally substituted with 1, 2 or 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, —OH, oxo, thiono, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy        having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,        —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—(C₁-C₄-halogenoalkyl)        having 1 to 5 halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having        1 to 5 halogen atoms, —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5        halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, Z¹⁹ and Z²⁰ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, halogen, C₁-C₄-alkyl and C₁-C₄-alkoxy,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, halogen, —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, —S—(C₁-C₄-alkyl) and a 4- to 6-membered heterocycloalkyl,        and    -   Z³ is selected from the group consisting of hydrogen, halogen,        C₁-C₄-alkyl, C₁-C₄-alkoxy and —N(C₁-C₄-alkyl)₂, or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5-membered heterocycloalkyl or a 5-membered        heteroaryl, each of which may be optionally substituted with one        or two substituents selected from the group consisting of        methyl, fluorine and oxo,    -   Z³ and Z⁵ are hydrogen, and    -   Z⁴ is selected from the group consisting of hydrogen and        C₁-C₄-alkoxy-C(O)—, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —NH—CO—C₁-C₄-alkyl, and monocyclic        heterocycles selected from the group of 4- to 7-membered        heterocycloalkyl or 5-membered heteroaryls having at least one        nitrogen atom via which the heteroaryl ring is connected to the        pyridine ring, each of which is optionally substituted with 1, 2        or 3 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is halogen, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and        C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, halogen, cyano, —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy,        —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, C₁-C₄-halogenoalkyl having 1        to 5 halogen atoms, C₁-C₄-halogenoalkoxy having 1 to 5 halogen        atoms, —S—(C₁-C₄-alkyl) and a 4- to 6-membered heterocycloalkyl,        and    -   Z³ is selected from the group consisting of hydrogen, halogen,        C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5        halogen atoms and —N(C₁-C₄-alkyl)₂, or    -   Z¹ and Z² form, together with the carbon atoms that they are        connected to, a 5-membered heterocycloalkyl or a 5-membered        heteroaryl, each of which may be optionally substituted with one        or two substituents selected from the group consisting of        methyl, fluorine and oxo,    -   Z³ and Z⁵ are hydrogen, and    -   Z⁴ is selected from the group consisting of hydrogen and        C₁-C₄-alkoxy-C(O)—, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:    -   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group        consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,        C₁-C₄-alkoxy, C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl),        —N(C₁-C₄-alkyl)₂, —NH—CO—C₁-C₄-alkyl, and monocyclic        heterocycles selected from the group of 4- to 7-membered        heterocycloalkyl or 5-membered heteroaryls having at least one        nitrogen atom via which the heteroaryl ring is connected to the        pyridine ring, each of which is optionally substituted with 1, 2        or 3 substituents independently selected from the group        consisting of halogen, cyano, nitro, —OH, oxo, thiono,        C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,        C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,        C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,        —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,        —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,        —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is halogen, or

-   Q is a 5-membered aromatic heterocycle of the formula (Q6)

-   -   in which:    -   T¹-T⁴ are independently selected from the group consisting of N,        O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O,        not more than one of T¹-T⁴ is S, not more than one of T¹-T⁴ is        N—Z²², and wherein    -   each Z²¹ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy, and    -   each Z²² is independently selected from the group consisting of        hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen        atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,        or

-   Q is a 5-membered aromatic heterocycle of the formula (Q7)

-   -   in which:    -   U¹-U⁴ are independently selected from the group consisting of N        and C—Z²³, wherein not more than three of U¹-U⁴ are N, and        wherein    -   each Z²³ is independently selected from the group consisting of        hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl        having 1 to 5 halogen atoms, C₁-C₄-alkoxy,        and stereoisomers, tautomers, N-oxides, hydrates, solvates, and        salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, methyl and methoxy,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, —OH, methyl, ethyl, —NHMe,        —NMe₂, trifluoromethyl, methoxy, trifluoromethoxy, —SMe and        morpholinyl, and    -   Z³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, methyl, methoxy and —NMe₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:

-   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group    consisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy,    ethoxy, isopropoxy, hydroxymethyl, NH₂, —NHMe —NMe₂, —NH—C(O)-Me,    morpholinyl, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is fluorine, chlorine, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²¹ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy and    -   Z²² is hydrogen, methyl, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy, or

-   Q is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, methyl, methoxy and        trifluoromethyl,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, —OH, cyano, methyl, ethyl,        tert-butyl, —NHMe, —NMe₂, trifluoromethyl, methoxy,        trifluoromethoxy, —SMe and morpholinyl, and    -   Z³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy        and —NMe₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:

-   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group    consisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy,    ethoxy, isopropoxy, hydroxymethyl, NH₂, —NHMe —NMe₂, —NH—C(O)-Me,    morpholinyl, or

-   Q is a pyridine ring of the formula (Q5)

-   -   in which:    -   Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and    -   Z²⁰ is fluorine, chlorine, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²¹ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy and    -   Z²² is hydrogen, methyl, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy, or

-   Q is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which:

-   Q is a substituted phenyl ring of the formula (Q1)

-   -   in which:    -   Z¹ and Z⁵ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, methyl, methoxy and        trifluoromethyl,    -   Z² and Z⁴ are independently selected from the group consisting        of hydrogen, fluorine, chlorine, —OH, cyano, methyl, ethyl,        tert-butyl, —NHMe, —NMe₂, trifluoromethyl, methoxy,        trifluoromethoxy, —SMe and morpholinyl, and    -   Z³ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy        and —NMe₂, or

-   Q is a pyridine ring of the formula (Q4)

-   -   in which:

-   Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the group    consisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy,    ethoxy, isopropoxy, hydroxymethyl, NH₂, —NHMe —NMe₂, —NH—C(O)-Me,    morpholinyl, or

-   Q is selected from the group consisting of

-   -   in which:    -   each Z²¹ is independently selected from the group consisting of        hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl,        methoxy and    -   Z²² is hydrogen, methyl, or

-   Q is selected from the group consisting of

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, and mixtures of same.

In a further embodiment of the first aspect, the present inventioncovers compounds of formula (I), supra, in which

-   A is A3 or A4

-   wherein-   R_(p) is selected from the group consisting of hydrogen,    C₁-C₄-alkyl; preferably hydrogen,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In a further aspect of the present invention in any or all of theembodiments according to the first to eighth aspect (including theembodiments under the heading “further embodiments of the first aspectof the present invention”) in the definition of X and/or Y “NR⁹” asdefined supra is excluded.

In a further aspect of the present invention in any or all of theembodiments according to the first to eighth aspect (including theembodiments under the heading “further embodiments of the first aspectof the present invention”) in the definition of R² hydrogen is excluded.

In a particular further embodiment of the first aspect, the presentinvention covers combinations of two or more of the above mentionedembodiments under the heading “further embodiments of the first aspectof the present invention”.

The present invention covers any sub-combination within any embodimentor aspect of the present invention of compounds of general formula (I),supra.

The present invention covers the compounds of general formula (I) whichare disclosed in the Example Section of this text, infra.

The compounds according to the invention of general formula (I) can beprepared according to the schemes 1a-e, 2, 3 and 4 as shown in theExperimental Section to the present invention (General Procedures). Theschemes and procedures described illustrate synthetic routes to thecompounds of general formula (I) of the invention and are not intendedto be limiting. It is clear to the person skilled in the art that theorder of transformations as exemplified in schemes 1a-e, 2 and 3 can bemodified in various ways. The order of transformations exemplified inthese schemes is therefore not intended to be limiting. In addition,interconversion of any of the substituents, Q, A, R¹, R², R³, R⁴, R⁵ orR⁶ can be achieved before and/or after the exemplified transformations.These modifications can be such as the introduction of protectinggroups, cleavage of protecting groups, reduction or oxidation offunctional groups, halogenation, metallation, substitution or otherreactions known to the person skilled in the art. These transformationsinclude those which introduce a functionality which allows for furtherinterconversion of substituents. Appropriate protecting groups and theirintroduction and cleavage are well-known to the person skilled in theart (see for example T. W. Greene and P. G. M. Wuts in Protective Groupsin Organic Synthesis, 3^(rd) edition, Wiley 1999). Specific examples aredescribed in the subsequent paragraphs.

In the following, several routes for the preparation of compounds ofgeneral formula (I) are described in schemes 1a-e and 2.

In accordance with a second aspect, the present invention covers methodsof preparing compounds of general formula (I) as defined supra, saidmethods comprising the step of allowing an intermediate compound ofgeneral formula 1N:

in which A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined for the compound ofgeneral formula (I) as defined supra,to react with a compound of general formula 1F:R²H  1F,in which R² is NR¹²R¹³, OR¹⁴, or SR¹⁵, each as defined for the compoundof general formula (I) as defined supra,thereby giving a compound of general formula (I):

in which A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined supra.In accordance with an alternative embodiment of the second aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1T:

in which A, R¹, R², R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, and in which Hal is halogen,particularly chlorine, bromine or iodine, to react with a compound ofgeneral formula 1H:Q-B(OR)₂  1H,in which Q is as defined for the compound of general formula (I) asdefined supra, and each R may be individually H or Me or both R arepinacolate, thereby giving a compound of general formula (I):

in which A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined supra.

In accordance with an alternative embodiment of the second aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1W:

in which Q, R², R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, to react with a compound ofgeneral formula 1M:

in which R¹ and A are as defined for the compound of general formula (I)as defined supra, thereby giving a compound of general formula (I):

in which A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined supra.

In accordance with an alternative embodiment of the second aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1X:

in which Q, A, R¹, R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, to react with a compound ofgeneral formula 1Y:R²H  1Y,in which R² is OR¹⁴ as defined for the compound of general formula (I)as defined supra, thereby giving a compound of general formula (I):

in which A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined supra and R² isC¹-C⁴-alkoxy which is optionally substituted as defined supra.

In accordance with an alternative embodiment of the second aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1N:

in which Q, A, R¹, R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, to react with a compound ofgeneral formula 2A:R²Met-X  2A,in which R² is C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of whichis optionally substituted as defined for the compound of general formula(I) as defined supra, Met is magnesium or zinc, and X is chlorine,bromine or iodine, thereby giving a compound of general formula (I):

in which A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined supra and R² isC₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl,C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of which is optionallysubstituted as defined supra.

In accordance with a third aspect, the present invention covers methodsof preparing compounds of general formula (I) as defined supra, saidmethods comprising the step of allowing an intermediate compound ofgeneral formula 1N:

in which A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined for the compound ofgeneral formula (I) as defined supra, to react with a compound ofgeneral formula 1F:R²H  1F,in which R² is NR¹²R¹³, OR¹⁴, or SR¹⁵, each as defined for the compoundof general formula (I) as defined supra,thereby giving a compound of general formula (I):

in which A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined supra, thenoptionally converting said compound into solvates, salts and/or solvatesof such salts using the corresponding (i) solvents and/or (ii) bases oracids.

In accordance with an alternative embodiment of the third aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1T:

in which A, R¹, R², R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, and in which Hal is halogen,particularly chlorine, bromine or iodine, to react with a compound ofgeneral formula 1H:Q-B(OR)₂  1H,in which Q is as defined for the compound of general formula (I) asdefined supra, and each R may be individually H or Me or both R arepinacolate,thereby giving a compound of general formula (I):

in which A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined supra, thenoptionally converting said compound into solvates, salts and/or solvatesof such salts using the corresponding (i) solvents and/or (ii) bases oracids.

In accordance with an alternative embodiment of the third aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1W:

in which Q, R², R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, to react with a compound ofgeneral formula 1M:

in which R¹ and A are as defined for the compound of general formula (I)as defined supra,thereby giving a compound of general formula (I):

in which A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined supra, thenoptionally converting said compound into solvates, salts and/or solvatesof such salts using the corresponding (i) solvents and/or (ii) bases oracids.

In accordance with an alternative embodiment of the third aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1X:

in which Q, A, R¹, R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra, to react with a compound ofgeneral formula 1Y:R²H  1Y,in which R² is OR¹⁴ as defined for the compound of general formula (I)as defined supra, thereby giving a compound of general formula (I):

in which A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined supra and R² isC₁-C₄-alkoxy which is optionally substituted as defined supra,then optionally converting said compound into solvates, salts and/orsolvates of such salts using the corresponding (i) solvents and/or (ii)bases or acids.

In accordance with an alternative embodiment of the third aspect, thepresent invention covers methods of preparing compounds of generalformula (I) as defined supra, said methods comprising the step ofallowing an intermediate compound of general formula 1N:

in which Q, A, R¹, R³, R⁴, R⁵ and R⁶ are as defined for the compound ofgeneral formula (I) as defined supra,in which R² is C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of whichis optionally substituted as defined for the compound of general formula(I) as defined supra, Met is magnesium or zinc, and X is chlorine,bromine or iodine,thereby giving a compound of general formula (I):

in which A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined supra and R² isC₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl,C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of which is optionallysubstituted as defined supra,then optionally converting said compound into solvates, salts and/orsolvates of such salts using the corresponding (i) solvents and/or (ii)bases or acids.

The present invention covers methods of preparing compounds of thepresent invention of general formula (I), said methods comprising thesteps as described in the Experimental Section herein.

In accordance with a fourth aspect, the present invention coversintermediate compounds which are useful for the preparation of thecompounds of general formula (I), supra.

Particularly, the inventions covers the intermediate compounds ofgeneral formula (II):

-   in which-   R² is —OH or as defined for the compound of general formula (I)    supra,-   R³, R⁴, R⁵, R⁶, and Q are as defined for the compound of general    formula (I) supra, and-   R^(A) is H or C₁-C₄-alkyl,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

Particularly, the inventions covers also the intermediate compounds ofgeneral formula (III):

-   in which-   R² is —OH or as defined for the compound of general formula (I)    supra,-   A, R¹, R³, R⁴, R⁵, and R⁶ are as defined for the compound of general    formula (I) supra, and-   Hal is halogen,    and stereoisomers, tautomers, N-oxides, hydrates, solvates, and    salts thereof, and mixtures of same.

In accordance with a fifth aspect, the present invention covers the useof said intermediate compounds for the preparation of a compound ofgeneral formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds ofgeneral formula (II):

-   in which-   R² is —OH or as defined for the compound of general formula (I)    supra,-   R³, R⁴, R⁵, R⁶, and Q are as defined for the compound of general    formula (I) supra, and-   R^(A) is H or C₁-C₄-alkyl,    for the preparation of a compound of general formula (I) as defined    supra.

Particularly, the inventions covers also the use of intermediatecompounds of general formula (III):

-   in which-   R² is —OH as defined for the compound of general formula (I) supra,-   A, R¹, R³, R⁴, R⁵, and R⁶ are as defined for the compound of general    formula (I) supra, and-   Hal is halogen,    for the preparation of a compound of general formula (I) as defined    supra.

The present invention covers the intermediate compounds which aredisclosed in the Example Section of this text, infra.

The compounds of general formula (I) of the present invention can beconverted to any salt, preferably pharmaceutically acceptable salts, asdescribed herein, by any method which is known to the person skilled inthe art. Similarly, any salt of a compound of general formula (I) of thepresent invention can be converted into the free compound, by any methodwhich is known to the person skilled in the art.

Compounds of general formula (I) of the present invention demonstrate avaluable pharmacological spectrum of action, which could not have beenpredicted. Compounds of the present invention have surprisingly beenfound to effectively interact with Slo-1 and it is possible thereforethat said compounds be used for the treatment or prevention of diseases,preferably helminthic infections, particularly of gastro-intestinal andextra-intestinal helminth infections, more particularly ofgastro-intestinal and extra-intestinal infections with nematodes inhumans and animals.

Compounds of the present invention can be utilized to control, treatand/or prevent helminth infections, in particular gastro-intestinal andextra-intestinal helminth infections. This method comprisesadministering to a mammal in need thereof an amount of a compound ofthis invention, or a pharmaceutically acceptable salt, isomer,polymorph, metabolite, hydrate, solvate or ester thereof; which iseffective to treat the disorder.

In an alternative aspect, this method comprises administering to birds,namely cage birds or in particular poultry, in need thereof an amount ofa compound of this invention, or a pharmaceutically acceptable salt,isomer, polymorph, metabolite, hydrate, solvate or ester thereof; whichis effective to treat the disorder.

Specifically in the field of veterinary medicine, compounds of thepresent invention are suitable, with favourable toxicity in warm bloodedanimals, for controlling parasites, in particular helminths, which occurin animal breeding and animal husbandry in livestock, breeding, zoo,laboratory, experimental and domestic animals. They are active againstall or specific stages of development of the parasites, in particular ofthe helminths.

Agricultural livestock include, for example, mammals, such as, sheep,goats, horses, donkeys, camels, buffaloes, rabbits, reindeers, fallowdeers, and in particular cattle and pigs; or poultry, such as turkeys,ducks, geese, and in particular chickens; or fish or crustaceans, e.g.in aquaculture.

Domestic animals include, for example, mammals, such as hamsters, guineapigs, rats, mice, chinchillas, ferrets or in particular dogs, cats; cagebirds; reptiles; amphibians or aquarium fish.

The present invention also provides methods of treating helminthinfections, particularly gastro-intestinal and extra-intestinal helminthinfections, more particularly gastro-intestinal and extra-intestinalinfections with nematodes.

These disorders have been well characterized in animals, and can betreated by administering pharmaceutical compositions of the presentinvention.

The term “treating” or “treatment” as used in the present text is usedconventionally, e.g., the management or care of a subject for thepurpose of combating, alleviating, reducing, relieving, improving thecondition of a disease or disorder, such as a nematode infection. Inparticular, and particularly in the animal health or veterinary field,the term “treating” or “treatment” includes prophylactic, metaphylacticor therapeutical treatment

Helminths pathogenic for humans or animals include, for example,acanthocephala, nematodes, pentastoma and platyhelmintha (e.g.monogenea, cestodes and trematodes).

Exemplary helminths include, without any limitation:

Monogenea: e.g.: Dactylogyrus spp., Gyrodactylus spp., Microbothriumspp., Polystoma spp., Troglocephalus spp.

Cestodes: from the order of the Pseudophyllidea, for example: Bothridiumspp., Diphyllobothrium spp., Diplogonoporus spp., Ichthyobothrium spp.,Ligula spp., Schistocephalus spp., Spirometra spp.

from the order of the Cyclophyllida, for example: Andyra spp.,Anoplocephala spp., Avitellina spp., Bertiella spp., Cittotaenia spp.,Davainea spp., Diorchis spp., Diplopylidium spp., Dipylidium spp.,Echinococcus spp., Echinocotyle spp., Echinolepis spp., Hydatigera spp.,Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp.,Paranoplocephala spp., Raillietina spp., Stilesia spp., Taenia spp.,Thysaniezia spp., Thysanosoma spp.

Trematodes: from the class of the Digenea, for example: Austrobilharziaspp., Brachylaima spp., Calicophoron spp., Catatropis spp., Clonorchisspp. Collyriclum spp., Cotylophoron spp., Cyclocoelum spp., Dicrocoeliumspp., Diplostomum spp., Echinochasmus spp., Echinoparyphium spp.,Echinostoma spp., Eurytrema spp., Fasciola spp., Fasciolides spp.,Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp.,Gigantobilharzia spp., Gigantocotyle spp., Heterophyes spp., Hypoderaeumspp., Leucochloridium spp., Metagonimus spp., Metorchis spp.,Nanophyetus spp., Notocotylus spp., Opisthorchis spp., Ornithobilharziaspp., Paragonimus spp., Paramphistomum spp., Plagiorchis spp.,Posthodiplostomum spp., Prosthogonimus spp., Schistosoma spp.,Trichobilharzia spp., Troglotrema spp., Typhlocoelum spp.

Nematodes: from the order of the Trichinellida, for example: Capillariaspp., Eucoleus spp. Paracapillaria spp., Trichinella spp.,Trichomosoides spp., Trichuris spp.

from the order of the Tylenchida, for example: Micronema spp.,Parastrongyloides spp. Strongyloides spp.

from the order of the Rhabditina, for example: Aelurostrongylus spp.,Amidostomum spp., Ancylostoma spp., Angiostrongylus spp., Bronchonemaspp., Bunostomum spp., Chabertia spp., Cooperia spp., Cooperioides spp.,Crenosoma spp., Cyathostomum spp., Cyclococercus spp., Cyclodontostomumspp., Cylicocyclus spp., Cylicostephanus spp., Cylindropharynx spp.,Cystocaulus spp., Dictyocaulus spp., Elaphostrongylus spp., Filaroidesspp., Globocephalus spp., Graphidium spp., Gyalocephalus spp.,Haemonchus spp., Heligmosomoides spp., Hyostrongylus spp., Marshallagiaspp., Metastrongylus spp., Muellerius spp., Necator spp., Nematodirusspp., Neostrongylus spp., Nippostrongylus spp., Obeliscoides spp.,Oesophagodontus spp., Oesophagostomum spp., Ollulanus spp.;Ornithostrongylus spp., Oslerus spp., Ostertagia spp., Paracooperiaspp., Paracrenosoma spp., Parafilaroides spp., Parelaphostrongylus spp.,Pneumocaulus spp., Pneumostrongylus spp., Poteriostomum spp.,Protostrongylus spp., Spicocaulus spp., Stephanurus spp., Strongylusspp., Syngamus spp., Teladorsagia spp., Trichonema spp.,Trichostrongylus spp., Triodontophorus spp., Troglostrongylus spp.,Uncinaria spp.from the order of the Spirurida, for example: Acanthocheilonema spp.,Anisakis spp., Ascaridia spp.; Ascaris spp., Ascarops spp., Aspiculurisspp., Baylisascaris spp., Brugia spp., Cercopithifilaria spp.,Crassicauda spp., Dipetalonema spp., Dirofilaria spp., Dracunculus spp.;Draschia spp., Enterobius spp., Filaria spp., Gnathostoma spp.,Gongylonema spp., Habronema spp., Heterakis spp.; Litomosoides spp., Loaspp., Onchocerca spp., Oxyuris spp., Parabronema spp., Parafilaria spp.,Parascaris spp., Passalurus spp., Physaloptera spp., Probstmayria spp.,Pseudofilaria spp., Setaria spp., Skjrabinema spp., Spirocerca spp.,Stephanofilaria spp., Strongyluris spp., Syphacia spp., Thelazia spp.,Toxascaris spp., Toxocara spp., Wuchereria spp.

Acantocephala: from the order of the Oligacanthorhynchida, for example:Macracanthorhynchus spp., Prosthenorchis spp.; from the order of theMoniliformida, for example: Moniliformis spp.

from the order of the Polymorphida, for example: Filicollis spp.; fromthe order of the Echinorhynchida, for example: Acanthocephalus spp.,Echinorhynchus spp., Leptorhynchoides spp.

Pentastoma: from the order of the Porocephalida, for example: Linguatulaspp.

The compounds of the present invention can be used in particular intherapy and prevention, i.e. prophylaxis, of helminth infections,particularly gastro-intestinal and extra-intestinal helminth infections,more particularly gastro-intestinal and extra-intestinal infections withnematodes.

By using the compounds of the present invention to control animalparasites, in particular helminths, it is intended to reduce or preventillness, cases of deaths and performance reductions (in the case ofmeat, milk, wool, hides, eggs, honey and the like), so that moreeconomical and simpler animal keeping is made possible and better animalwell-being is achievable.

The term “control” or “controlling”, as used herein with regard to theanimal health field, means that the compounds of the present inventionare effective in reducing the incidence of the respective parasite in ananimal infected with such parasites to innocuous levels. Morespecifically, “controlling”, as used herein, means that the compounds ofthe present invention are effective in killing the respective parasite,inhibiting its growth, or inhibiting its proliferation.

In accordance with a further aspect, the present invention coverscompounds of general formula (I), as described supra, or stereoisomers,tautomers, N-oxides, hydrates, solvates, and salts thereof, particularlypharmaceutically acceptable salts thereof, or mixtures of same, for usein the treatment or prevention of diseases, in particular of helminthinfections, particularly of gastro-intestinal and extra-intestinalhelminth infections, more particularly of gastro-intestinal andextra-intestinal infections with nematodes.

The pharmaceutical activity of the compounds according to the inventioncan be explained by their interaction with the Slo-1 ion channel.

In accordance with a further aspect, the present invention covers theuse of compounds of general formula (I), as described supra, orstereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, particularly pharmaceutically acceptable salts thereof, ormixtures of same, for the treatment or prevention of diseases, inparticular of helminth infections, particularly of gastro-intestinal andextra-intestinal helminth infections, more particularly ofgastro-intestinal and extra-intestinal infections with nematodes.

In accordance with a further aspect, the present invention covers theuse of compounds of general formula (I), as described supra, orstereoisomers, tautomers, N-oxides, hydrates, solvates, and saltsthereof, particularly pharmaceutically acceptable salts thereof, ormixtures of same, in a method of treatment or prevention of diseases, inparticular of helminth infections, particularly of gastro-intestinal andextra-intestinal helminth infections, more particularly ofgastro-intestinal and extra-intestinal infections with nematodes.

In accordance with a further aspect, the present invention covers use ofa compound of general formula (I), as described supra, or stereoisomers,tautomers, N-oxides, hydrates, solvates, and salts thereof, particularlypharmaceutically acceptable salts thereof, or mixtures of same, for thepreparation of a pharmaceutical composition, preferably a medicament,for the prevention or treatment of diseases, in particular of helminthinfections, particularly of gastro-intestinal and extra-intestinalhelminth infections, more particularly of gastro-intestinal andextra-intestinal infections with nematodes.

In accordance with a further aspect, the present invention covers amethod of treatment or prevention of diseases, in particular of helminthinfections, particularly of gastro-intestinal and extra-intestinalhelminth infections, more particularly of gastro-intestinal andextra-intestinal infections with nematodes, using an effective amount ofa compound of general formula (I), as described supra, or stereoisomers,tautomers, N-oxides, hydrates, solvates, and salts thereof, particularlypharmaceutically acceptable salts thereof, or mixtures of same.

In accordance with a further aspect, the present invention coverscompounds of general formula (I), as described supra, or stereoisomers,tautomers, N-oxides, hydrates, solvates, and salts thereof, particularlypharmaceutically acceptable salts thereof, or mixtures of same, for useas an antiendoparasitical agent.

In accordance with a further aspect, the present invention coverscompounds of general formula (I), as described supra, or stereoisomers,tautomers, N-oxides, hydrates, solvates, and salts thereof, particularlypharmaceutically acceptable salts thereof, or mixtures of same, for useas a anthelmintic agent, in particular for use as a nematicidal agent, aplatyhelminthicidal agent, an acanthocephalicidal agent, or apentastomicidal agent.

In accordance with a further aspect, the present invention coverspharmaceutical compositions, in particular a veterinary formulation,comprising a compound of general formula (I), as described supra, or astereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, a saltthereof, particularly a pharmaceutically acceptable salt, or a mixtureof same, and one or more excipients), in particular one or morepharmaceutically acceptable excipient(s). Conventional procedures forpreparing such pharmaceutical compositions in appropriate dosage formscan be utilized.

In accordance with a further aspect, the present invention covers amethod for preparing a pharmaceutical composition, in particular aveterinary formulation, comprising the step of mixing a compound ofgeneral formula (I), as described supra, or a stereoisomer, a tautomer,an N-oxide, a hydrate, a solvate, a salt thereof, particularly apharmaceutically acceptable salt, or a mixture of same, with one or moreexcipients), in particular one or more pharmaceutically acceptableexcipient(s).

In accordance with a further aspect, the present invention covers amethod of treatment or prevention of diseases, in particular of helminthinfections, particularly of gastro-intestinal and extra-intestinalhelminth infections, more particularly of gastro-intestinal andextra-intestinal infections with nematodes, using a pharmaceuticalcomposition, in particular a veterinary formulation, comprising aneffective amount of a compound of general formula (I), as describedsupra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, andsalts thereof, particularly pharmaceutically acceptable salts thereof,or mixtures of same.

The present invention furthermore covers pharmaceutical compositions, inparticular veterinary formulations, which comprise at least one compoundaccording to the invention, conventionally together with one or morepharmaceutically suitable excipients, and to their use for the abovementioned purposes.

It is possible for the compounds according to the invention to havesystemic and/or local activity. For this purpose, they can beadministered in a suitable manner, such as, for example, via the oral,parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal,vaginal, dermal, transdermal, conjunctival, otic route or as an implantor stent. Such administration can be carried out prophylactically,methaphylactically or therapeutically.

For these administration routes, it is possible for the compoundsaccording to the invention to be administered in suitable administrationforms.

For oral administration, it is possible to formulate the compoundsaccording to the invention to dosage forms known in the art that deliverthe compounds of the invention rapidly and/or in a modified manner, suchas, for example, tablets (uncoated or coated tablets, for example withenteric or controlled release coatings that dissolve with a delay or areinsoluble), orally-disintegrating tablets, films/wafers,films/lyophylisates, capsules (for example hard or soft gelatinecapsules), sugar-coated tablets, granules, pellets, chewables (forexample soft chewables), powders, emulsions, suspensions, aerosols orsolutions. It is possible to incorporate the compounds according to theinvention in crystalline and/or amorphised and/or dissolved form intosaid dosage forms.

Parenteral administration can be effected with avoidance of anabsorption step (for example intravenous, intraarterial, intracardial,intraspinal or intralumbal) or with inclusion of absorption (for exampleintramuscular, subcutaneous, intracutaneous, percutaneous orintraperitoneal).

Administration forms which are suitable for parenteral administrationare, inter alia, preparations for injection and infusion in the form ofsolutions, suspensions, emulsions, lyophylisates or sterile powders.

Examples which are suitable for other administration routes arepharmaceutical forms for inhalation [inter alia powder inhalers,nebulizers], nasal drops, nasal solutions, nasal sprays;

tablets/films/wafers/capsules for lingual, sublingual or buccaladministration; suppositories; eye drops, eye ointments, eye baths,ocular inserts, ear drops, ear sprays, ear powders, ear-rinses, eartampons; vaginal capsules, aqueous suspensions (lotions, mixtureagitandae), lipophilic suspensions, emulsions, ointments, creams,transdermal therapeutic systems (such as, for example, patches), milk,pastes, foams, spot-ons, dusting powders, implants or stents.

The compounds according to the invention can be incorporated into thestated administration forms. This can be effected in a manner known perse by mixing with pharmaceutically suitable excipients. Pharmaceuticallysuitable excipients include, inter alia,

-   -   fillers and carriers (for example cellulose, microcrystalline        cellulose (such as, for example, Avicel®, lactose, mannitol,        starch, calcium phosphate (such as, for example, Di-Cafos®)),    -   ointment bases (for example petroleum jelly, paraffins,        triglycerides, waxes, wool wax, wool wax alcohols, lanolin,        hydrophilic ointment, polyethylene glycols),    -   bases for suppositories (for example polyethylene glycols, cacao        butter, hard fat),    -   solvents (for example water, ethanol, isopropanol, glycerol,        propylene glycol, medium chain-length triglycerides fatty oils,        liquid polyethylene glycols, paraffins),    -   surfactants, emulsifiers, dispersants or wetters (for example        sodium dodecyl sulfate), lecithin, phospholipids, fatty alcohols        (such as, for example, Lanette®), sorbitan fatty acid esters        (such as, for example, Span®), polyoxyethylene sorbitan fatty        acid esters (such as, for example, Tween®), polyoxyethylene        fatty acid glycerides (such as, for example, Cremophor®),        polyoxethylene fatty acid esters, polyoxyethylene fatty alcohol        ethers, glycerol fatty acid esters, poloxamers (such as, for        example, Pluronic®),    -   buffers, acids and bases (for example phosphates, carbonates,        citric acid, acetic acid, hydrochloric acid, sodium hydroxide        solution, ammonium carbonate, trometamol, triethanolamine),    -   isotonicity agents (for example glucose, sodium chloride),    -   adsorbents (for example highly-disperse silicas),    -   viscosity-increasing agents, gel formers, thickeners and/or        binders (for example polyvinylpyrrolidone, methylcellulose,        hydroxypropylmethylcellulose, hydroxypropyl-cellulose,        carboxymethylcellulose-sodium, starch, carbomers, polyacrylic        acids (such as, for example, Carbopol®); alginates, gelatine),    -   disintegrants (for example modified starch,        carboxymethylcellulose-sodium, sodium starch glycolate (such as,        for example, Explotab®), cross-linked polyvinylpyrrolidone,        croscarmellose-sodium (such as, for example, AcDiSol®)),    -   flow regulators, lubricants, glidants and mould release agents        (for example magnesium stearate, stearic acid, talc,        highly-disperse silicas (such as, for example, Aerosil®),    -   coating materials (for example sugar, shellac) and film formers        for films or diffusion membranes which dissolve rapidly or in a        modified manner (for example polyvinylpyrrolidones (such as, for        example, Kollidon®), polyvinyl alcohol,        hydroxypropylmethylcellulose, hydroxypropylcellulose,        ethylcellulose, hydroxypropyl-methylcellulose phthalate,        cellulose acetate, cellulose acetate phthalate, polyacrylates,        polymethacrylates such as, for example, Eudragit®)),    -   capsule materials (for example gelatine,        hydroxypropylmethylcellulose),    -   synthetic polymers (for example polylactides, polyglycolides,        polyacrylates, polymethacrylates (such as, for example,        Eudragit®), polyvinylpyrrolidones (such as, for example,        Kollidon®), polyvinyl alcohols, polyvinyl acetates, polyethylene        oxides, polyethylene glycols and their copolymers and        blockcopolymers),    -   plasticizers (for example polyethylene glycols, propylene        glycol, glycerol, triacetine, triacetyl citrate, dibutyl        phthalate),    -   penetration enhancers,    -   stabilisers (for example antioxidants such as, for example,        ascorbic acid, ascorbyl palmitate, sodium ascorbate,        butylhydroxyanisole, butylhydroxytoluene, propyl gallate),    -   preservatives (for example parabens, sorbic acid, thiomersal,        benzalkonium chloride, chlorhexidine acetate, sodium benzoate),    -   colourants (for example inorganic pigments such as, for example,        iron oxides, titanium dioxide),    -   flavourings, sweeteners, flavour- and/or odour-masking agents.

The present invention furthermore relates to a pharmaceuticalcomposition which comprise at least one compound according to theinvention, conventionally together with one or more pharmaceuticallysuitable excipient(s), and to their use according to the presentinvention.

In accordance with another aspect, the present invention coverspharmaceutical combinations, in particular medicaments, comprising atleast one compound of general formula (I) of the present invention andat least one or more further active ingredients, in particular for thetreatment and/or prevention of an endo- and/or ectoparasiticidalinfection.

The term “endoparasite” in the present invention is used as known topersons skilled in the art, and refers in particular to helminths. Theterm “ectoparasite” in the present invention is used as known to personsskilled in the art, and refers in particular to arthropods, particularlyinsects or acarids.

Particularly, the present invention covers a pharmaceutical combination,in particular a veterinary combination, which comprises:

-   -   one or more first active ingredients, in particular compounds of        general formula (I) as defined supra, and    -   one or more further active ingredients, in particular one or        more endo- and/or ectoparasiticides.

The term “combination” in the present invention is used as known topersons skilled in the art, it being possible for said combination to bea fixed combination, a non-fixed combination or a kit-of-parts.

A “fixed combination” in the present invention is used as known topersons skilled in the art and is defined as a combination wherein, forexample, a first active ingredient, such as one or more compounds ofgeneral formula (I) of the present invention, and a further activeingredient are present together in one unit dosage or in one singleentity. One example of a “fixed combination” is a pharmaceuticalcomposition wherein a first active ingredient and a further activeingredient are present in admixture for simultaneous administration,such as in a formulation. Another example of a “fixed combination” is apharmaceutical combination wherein a first active ingredient and afurther active ingredient are present in one unit without being inadmixture.

A non-fixed combination or “kit-of-parts” in the present invention isused as known to persons skilled in the art and is defined as acombination wherein a first active ingredient and a further activeingredient are present in more than one unit. One example of a non-fixedcombination or kit-of-parts is a combination wherein the first activeingredient and the further active ingredient are present separately. Itis possible for the components of the non-fixed combination orkit-of-parts to be administered separately, sequentially,simultaneously, concurrently or chronologically staggered.

The compounds of the present invention can be administered as the solepharmaceutical agent or in combination with one or more otherpharmaceutically active ingredients where the combination causes nounacceptable adverse effects. The present invention also covers suchpharmaceutical combinations. For example, the compounds of the presentinvention can be combined with known ectoparasiticides and/orendoparasiticides.

The other or further active ingredients specified herein by their commonnames are known and described, for example, in the Pesticide Manual(“The Pesticide Manual” 16th Ed., British Crop Protection Council 2012)or can be searched in the internet (e.g.http://www.alanwood.net/pesticides). The classification is based on thecurrent IRAC Mode of Action Classification Scheme at the time of filingof this patent application.

Examples of ectoparasiticides and/or endoparasiticides are insecticides,acaricides and nematicides, and include in particular:

(1) Acetylcholinesterase (AChE) inhibitors, such as, for example,carbamates, for example alanycarb, aldicarb, bendiocarb, benfuracarb,butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan,ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb,methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur,thiodicarb, thiofanox, triazamate, trimethacarb, XMC and xylylcarb; ororganophosphates, for example acephate, azamethiphos, azinphos-ethyl,azinphos-methyl, cadusafos, chlorethoxyfos, chlorfenvinphos,chlormephos, chlorpyrifos-methyl, coumaphos, cyanophos,demeton-S-methyl, diazinon, dichlorvos/DDVP, dicrotophos, dimethoate,dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur,fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imicyafos,isofenphos, isopropyl O-(methoxyaminothiophosphoryl) salicylate,isoxathion, malathion, mecarbam, methamidophos, methidathion, mevinphos,monocrotophos, naled, omethoate, oxydemeton-methyl, parathion-methyl,phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim,pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos,pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos,tetrachlorvinphos, thiometon, triazophos, triclorfon and vamidothion.

(2) GABA-gated chloride channel blockers, such as, for example,cyclodiene-organochlorines, for example chlordane and endosulfan orphenylpyrazoles (fiproles), for example ethiprole and fipronil.

(3) Sodium channel modulators, such as, for example, pyrethroids, e.g.acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin,bifenthrin, bioallethrin, bioallethrin s-cyclopentenyl isomer,bioresmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin,lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin,beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin[(1R)-trans-isomer], deltamethrin, empenthrin [(EZ)-(1R)-isomer],esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate,flumethrin, tau-fluvalinate, halfenprox, imiprothrin, kadethrin,momfluorothrin, permethrin, phenothrin [(1R)-trans-isomer], prallethrin,pyrethrins (pyrethrum), resmethrin, silafluofen, tefluthrin,tetramethrin, tetramethrin [(1R)-isomer)], tralomethrin andtransfluthrin or DDT or methoxychlor.

(4) Nicotinic acetylcholine receptor (nAChR) competitive modulators,such as, for example, neonicotinoids, e.g. acetamiprid, clothianidin,dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam ornicotine or sulfoxaflor or flupyradifurone.

(5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators, suchas, for example, spinosyns, e.g. spinetoram and spinosad.

(6) Glutamate-gated chloride channel (GIuCl) allosteric modulators, suchas, for example, avermectins/milbemycins, for example abamectin,emamectin benzoate, lepimectin and milbemectin.

(7) Juvenile hormone mimics, such as, for example, juvenile hormoneanalogues, e.g. hydroprene, kinoprene and methoprene or fenoxycarb orpyriproxyfen.

(9) Modulators of Chordotonal Organs, such as, for example pymetrozineor flonicamid.

(10) Mite growth inhibitors, such as, for example clofentezine,hexythiazox and diflovidazin or etoxazole.

(12) Inhibitors of mitochondrial ATP synthase, such as, ATP disruptorssuch as, for example, diafenthiuron or organotin compounds, for exampleazocyclotin, cyhexatin and fenbutatin oxide or propargite or tetradifon.

(13) Uncouplers of oxidative phosphorylation via disruption of theproton gradient, such as, for example, chlorfenapyr, DNOC andsulfluramid.

(14) Nicotinic acetylcholine receptor channel blockers, such as, forexample, bensultap, cartap hydrochloride, thiocylam, andthiosultap-sodium.

(15) Inhibitors of chitin biosynthesis, type 0, such as, for example,bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron,flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron,teflubenzuron and triflumuron.

(16) Inhibitors of chitin biosynthesis, type 1, for example buprofezin.

(17) Moulting disruptor (in particular for Diptera, i.e. dipterans),such as, for example, cyromazine.

(18) Ecdysone receptor agonists, such as, for example, chromafenozide,halofenozide, methoxyfenozide and tebufenozide.

(19) Octopamine receptor agonists, such as, for example, amitraz.

(20) Mitochondrial complex III electron transport inhibitors, such as,for example, hydramethylnone or acequinocyl or fluacrypyrim.

(21) Mitochondrial complex I electron transport inhibitors, such as, forexample from the group of the METI acaricides, e.g. fenazaquin,fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad and tolfenpyrad orrotenone (Derris).

(22) Voltage-dependent sodium channel blockers, such as, for exampleindoxacarb or metaflumizone.

(23) Inhibitors of acetyl CoA carboxylase, such as, for example,tetronic and tetramic acid derivatives, e.g. spirodiclofen, spiromesifenand spirotetramat.

(25) Mitochondrial complex II electron transport inhibitors, such as,for example, beta-ketonitrile derivatives, e.g. cyenopyrafen andcyflumetofen and carboxanilides, such as, for example, pyflubumide.

(28) Ryanodine receptor modulators, such as, for example, diamides, e.g.chlorantraniliprole, cyantraniliprole and flubendiamide, further activeingredients such as, for example, Afidopyropen, Afoxolaner,Azadirachtin, Benclothiaz, Benzoximate, Bifenazate, Broflanilide,Bromopropylate, Chinomethionat, Chloroprallethrin, Cryolite,Cyclaniliprole, Cycloxaprid, Cyhalodiamide, Dicloromezotiaz, Dicofol,epsilon-Metofluthrin, epsilon-Momfluthrin, Flometoquin,Fluazaindolizine, Fluensulfone, Flufenerim, Flufenoxystrobin,Flufiprole, Fluhexafon, Fluopyram, Fluralaner, Fluxametamide,Fufenozide, Guadipyr, Heptafluthrin, Imidaclothiz, Iprodione,kappa-Bifenthrin, kappa-Tefluthrin, Lotilaner, Meperfluthrin,Paichongding, Pyridalyl, Pyrifluquinazon, Pyriminostrobin,Spirobudiclofen, Tetramethylfluthrin, Tetraniliprole,Tetrachlorantraniliprole, Tioxazafen, Thiofluoximate, Triflumezopyrimand iodomethane; furthermore preparations based on Bacillus firmus(1-1582, BioNeem, Votivo), and also the following compounds:1-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazole-5-amine(known from WO2006/043635) (CAS 885026-50-6),{1′-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]-5-fluorospiro[indol-3,4′-piperidin]-1(2H)-yl}(2-chloropyridin-4-yl)methanone(known from WO2003/106457) (CAS 637360-23-7),2-chloro-N-[2-{1-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]piperidin-4-yl}-4-(trifluoromethyl)phenyl]isonicotinamide(known from WO2006/003494) (CAS 872999-66-1),3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one(known from WO 2010052161) (CAS 1225292-17-0),3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-ylethyl carbonate (known from EP2647626) (CAS 1440516-42-6),4-(but-2-yn-1-yloxy)-6-(3,5-dimethylpiperidin-1-yl)-5-fluoropyrimidine(known from WO2004/099160) (CAS 792914-58-0), PF1364 (known fromJP2010/018586) (CAS 1204776-60-2),N-[(2E)-1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(known from WO2012/029672) (CAS 1363400-41-2),(3E)-3-[1-[(6-chloro-3-pyridyl)methyl]-2-pyridylidene]-1,1,1-trifluoro-propan-2-one(known from WO2013/144213) (CAS 1461743-15-6),N-[3-(benzylcarbamoyl)-4-chlorophenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide(known from WO2010/051926) (CAS 1226889-14-0),5-bromo-4-chloro-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloro-2-pyridyl)pyrazole-3-carboxamide(known from CN103232431) (CAS 1449220-44-3),4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxido-3-thietanyl)-benzamide,4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(trans-1-oxido-3-thietanyl)-benzamideand4-[(5S)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxido-3-thietanyl)benzamide(known from WO 2013/050317 A1) (CAS 1332628-83-7),N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propanamide,(+)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propanamideand(−)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propanamide(known from WO 2013/162715 A2, WO 2013/162716 A2, US 2014/0213448 A1)(CAS 1477923-37-7),5-[[(2E)-3-chloro-2-propen-1-yl]amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(known from CN 101337937 A) (CAS 1105672-77-2),3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)thioxomethyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide,(Liudaibenjiaxuanan, known from CN 103109816 A) (CAS 1232543-85-9);N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1H-Pyrazole-5-carboxamide(known from WO 2012/034403 A1) (CAS 1268277-22-0),N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide(known from WO 2011/085575 A1) (CAS 1233882-22-8),4-[3-[2,6-dichloro-4-[(3,3-dichloro-2-propen-1-yl)oxy]phenoxy]propoxy]-2-methoxy-6-(trifluoromethyl)-pyrimidine (knownfrom CN 101337940 A) (CAS 1108184-52-6); (2E)- and2(Z)-2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]-hydrazinecarboxamide(known from CN 101715774 A) (CAS 1232543-85-9);3-(2,2-dichloroethenyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl-cyclopropanecarboxylicacid ester (known from CN 103524422 A) (CAS 1542271-46-4);(4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]-indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylicacid methyl ester (known from CN 102391261 A) (CAS 1370358-69-2);6-deoxy-3-O-ethyl-2,4-di-O-methyl-,1-[N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1H-1,2,4-triazol-3-yl]phenyl]carbamate]-α-L-mannopyranose(known from US 2014/0275503 A1) (CAS 1181213-14-8);8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane(CAS 1253850-56-4),(8-anti)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane(CAS 933798-27-7),(8-syn)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane(known from WO 2007040280 A1, WO 2007040282 A1) (CAS 934001-66-8),N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)thio]-propanamide(known from WO 2015/058021 A1, WO 2015/058028 A1) (CAS 1477919-27-9),N-[4-(aminothioxomethyl)-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide(known from CN 103265527 A) (CAS 1452877-50-7),5-(1,3-dioxan-2-yl)-4-[[4-(trifluoromethyl)phenyl]methoxy]-pyrimidine(known from WO 2013/115391 A1) (CAS 1449021-97-9),3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diazaspiro[4.5]dec-3-en-2-one(known from WO 2010/066780 A1, WO 2011/151146 A1) (CAS 1229023-34-0),3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-1,8-diazaspiro[4.5]decane-2,4-dione(known from WO 2014/187846 A1) (CAS 1638765-58-8),3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl-carbonicacid ethyl ester (known from WO 2010/066780 A1, WO 2011151146 A1) (CAS1229023-00-0),N-[1-[(6-chloro-3-pyridinyl)methyl]-2(1H)-pyridinylidene]-2,2,2-trifluoro-acetamide(known from DE 3639877 A1, WO 2012029672 A1) (CAS 1363400-41-2),[N(E)]-N-[1-[(6-chloro-3-pyridinyl)methyl]-2(1H)-pyridinylidene]-2,2,2-trifluoro-acetamide, (known from WO2016005276 A1) (CAS 1689566-03-7),[N(Z)]—N-[1-[(6-chloro-3-pyridinyl)methyl]-2(1H)-pyridinylidene]-2,2,2-trifluoro-acetamide,(CAS 1702305-40-5),3-endo-3-[2-propoxy-4-(trifluoromethyl)phenoxy]-9-[[5-(trifluoromethyl)-2-pyridinyl]oxy]-9-azabicyclo[3.3.1]nonane(known from WO 2011/105506 A1, WO 2016/133011 A1) (CAS 1332838-17-1).

Active ingredients with unknown or non-specific mode of action, e.g.,fentrifanil, fenoxacrim, cycloprene, chlorobenzilate, chlordimeform,flubenzimine, dicyclanil, amidoflumet, quinomethionate, triarathene,clothiazoben, tetrasul, potassium oleate, petroleum, metoxadiazone,gossyplure, flutenzin, bromopropylate, cryolite;

Active ingredients from other classes, e.g. butacarb, dimetilan,cloethocarb, phosphocarb, pirimiphos (-ethyl), parathion (-ethyl),methacrifos, isopropyl o-salicylate, trichlorfon, sulprofos, propaphos,sebufos, pyridathion, prothoate, dichlofenthion,demeton-S-methylsulphone, isazofos, cyanofenphos, dialifos,carbophenothion, autathiofos, aromfenvinfos (-methyl), azinphos(-ethyl), chlorpyrifos (-ethyl), fosmethilan, iodofenphos,dioxabenzofos, formothion, fonofos, flupyrazofos, fensulfothion,etrimfos;

organochlorines, e.g. camphechlor, lindane, heptachlor; orphenylpyrazoles, e.g. acetoprole, pyrafluprole, pyriprole, vaniliprole,sisapronil; or isoxazolines, e.g. sarolaner, afoxolaner, lotilaner,fluralaner;

pyrethroids, e.g. (cis-, trans-), metofluthrin, profluthrin, flufenprox,flubrocythrinate, fubfenprox, fenfluthrin, protrifenbute, pyresmethrin,RU15525, terallethrin, cis-resmethrin, heptafluthrin, bioethanomethrin,biopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin,clocythrin, cyhalothrin (lambda-), chlovaporthrin, or halogenatedcarbonhydrogen compounds (HCHs);neonicotinoids, e.g. nithiazine;dicloromezotiaz, triflumezopyrim;macrocyclic lactones, e.g. nemadectin, ivermectin, latidectin,moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate;milbemycin oxime;triprene, epofenonane, diofenolan;

Biologicals, hormones or pheromones, for example natural products, e.g.thuringiensin, codlemone or neem components;

dinitrophenols, e.g. dinocap, dinobuton, binapacryl;

benzoylureas, e.g. fluazuron, penfluron;

amidine derivatives, e.g. chlormebuform, cymiazole, demiditraz;

Bee hive varroa acaricides, for example organic acids, e.g. formic acid,oxalic acid.

Non-limiting examples of insecticides and acaricides of particularinterest for use in animal health are and include in particular [i.e.Mehlhorn et al Encyclpaedic Reference of Parasitology 4th edition (ISBN978-3-662-43978-4)]:

Effectors at arthropod ligand gated chloride channels: chlordane,heptachlor, endoculfan. Dieldrin, bromocyclen, toxaphene, lindane,fipronil, pyriprole, sisapronil, afoxolaner, fluralaner, sarolaner,lotilaner, fluxametamide, broflanilide, avermectin, doramectin,eprinomectin, ivermectin, milbemycin, moxidectin, selamectin;

Modulators of arthropod octopaminergic receptors: amitraz, BTS27271,cymiazole, demiditraz;

Effectors at arthropod voltage-gated sodium channels: DDT, methoxychlor,metaflumizone, indoxacarb, cinerin I, cinerin II, jasmolin I, jasmolinII, pyrethrin I, pyrethrin II, allethrin, alphacypermethrin,bioallethrin, betacyfluthrin, cyfluthrin, cyhalothrin, cypermethrin,deltamethrin, etofenprox, fenvalerate, flucythrinate, flumethrin,halfenprox, permethrin, phenothrin, resmethrin, tau-fluvalinate,tetramethrin;

Effectors at arthropod nicotinic cholinergic synapses (acetylcholineesterase, acetylcholine receptors): bromoprypylate, bendiocarb,carbaryl, methomyl, promacyl, propoxur, azamethiphos, chlorfenvinphos,chlorpyrifos, coumaphos, cythioate, diazinon, diclorvos, dicrotophos,dimethoate, ethion, famphur, fenitrothion, fenthion, heptenophos,malathion, naled, phosmet, phoxim, phtalofos, propetamphos, temephos,tetrachlorvinphos, trichlorfon, imidacloprid, nitenpyram, dinotefuran,spinosad, spinetoram;

Effectors on arthropod development processes: cyromazine, dicyclanil,diflubenzuron, fluazuron, lufenuron, triflumuron, fenoxycarb,hydroprene, methoprene, pyriproxyfen, fenoxycarb, hydroprene,S-methoprene, pyriproxyfen.

Exemplary active ingredients from the group of endoparasiticides, as afurther or other active ingredient in the present invention, include,without limitation, anthelmintically active compounds and antiprotozoalactive compounds.

Anthelmintically active compounds, including, without limitation, thefollowing nematicidally, trematicidally and/or cestocidally activecompounds:

from the class of macrocyclic lactones, for example: eprinomectin,abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin,latidectin, milbemectin, ivermectin, emamectin, milbemycin;

from the class of benzimidazoles and probenzimidazoles, for example:oxibendazole, mebendazole, triclabendazole, thiophanate, parbendazole,oxfendazole, netobimin, fenbendazole, febantel, thiabendazole,cyclobendazole, cambendazole, albendazole-sulphoxide, albendazole,flubendazole;from the class of depsipeptides, preferably cyclic depsipetides, inparticular 24-membered cyclic depsipeptides, for example: emodepside,PF1022A;from the class of tetrahydropyrimidines, for example: morantel,pyrantel, oxantel;from the class of imidazothiazoles, for example: butamisole, levamisole,tetramisole;from the class of aminophenylamidines, for example: amidantel,deacylated amidantel (dAMD), tribendimidine;from the class of aminoacetonitriles, for example: monepantel;from the class of paraherquamides, for example: paraherquamide,derquantel;from the class of salicylanilides, for example: tribromsalan,bromoxanide, brotianide, clioxanide, closantel, niclosamide,oxyclozanide, rafoxanide;from the class of substituted phenols, for example: nitroxynil,bithionol, disophenol, hexachlorophene, niclofolan, meniclopholan;from the class of organophosphates, for example: trichlorfon,naphthalofos, dichlorvos/DDVP, crufomate, coumaphos, haloxon;from the class of piperazinones/quinolines, for example: praziquantel,epsiprantel;from the class of piperazines, for example: piperazine, hydroxyzine;from the class of tetracyclines, for example: tetracyclin,chlorotetracycline, doxycyclin, oxytetracyclin, rolitetracyclin;from diverse other classes, for example: bunamidine, niridazole,resorantel, omphalotin, oltipraz, nitroscanate, nitroxynile,oxamniquine, mirasan, miracil, lucanthone, hycanthone, hetolin, emetine,diethylcarbamazine, dichlorophen, diamfenetide, clonazepam, bephenium,amoscanate, clorsulon.

Antiprotozoal active ingredients in the present invention, including,without limitation, the following active ingredients:

from the class of triazines, for example: diclazuril, ponazuril,letrazuril, toltrazuril;

from the class of polylether ionophore, for example: monensin,salinomycin, maduramicin, narasin;

from the class of macrocyclic lactones, for example: milbemycin,erythromycin;

from the class of quinolones, for example: enrofloxacin, pradofloxacin;

from the class of quinines, for example: chloroquine;

from the class of pyrimidines, for example: pyrimethamine;

from the class of sulfonamides, for example: sulfaquinoxaline,trimethoprim, sulfaclozin;

from the class of thiamines, for example: amprolium;

from the class of lincosamides, for example: clindamycin;

from the class of carbanilides, for example: imidocarb;

from the class of nitrofuranes, for example: nifurtimox;

from the class of quinazolinone alkaloids, for example: halofuginon;

from diverse other classes, for example: oxamniquin, paromomycin;

from the class of vaccines or antigenes from microorganisms, forexample: Babesia canis rossi, Eimeria tenella, Eimeria praecox, Eimerianecatrix, Eimeria mitis, Eimeria maxima, Eimeria brunetti, Eimeriaacervulina, Babesia canis vogeli, Leishmania infantum, Babesia caniscanis, Dictyocaulus viviparus.

All named other or further active ingredients in the present inventioncan, if their functional groups enable this, optionally form salts withsuitable bases or acids.

Based upon standard laboratory techniques known to evaluate compoundsuseful for the treatment of helminth infections, by standard toxicitytests and by standard pharmacological assays for the determination oftreatment of the conditions identified above in animals, and bycomparison of these results with the results of known active ingredientsor medicaments that are used to treat these conditions, the effectivedosage of the compounds of the present invention can readily bedetermined for treatment of each desired indication. The amount of theactive ingredient to be administered in the treatment of one of theseconditions can vary widely according to such considerations as theparticular compound and dosage unit employed, the mode ofadministration, the period of treatment, the age and sex of the subjecttreated, and the nature and extent of the condition treated.

The total amount of the active ingredient to be administered willgenerally range from about 0.001 mg/kg to about 200 mg/kg body weightper day, and preferably from about 0.01 mg/kg to about 20 mg/kg bodyweight per day. Clinically useful dosing schedules will range from oneto three times a day dosing to once every four weeks dosing. Inaddition, it is possible for “drug holidays”, in which a subject is notdosed with a drug for a certain period of time, to be beneficial to theoverall balance between pharmacological effect and tolerability.Furthermore, it is possible to have long-acting treatments, wherein thesubject gets treated once for more than four weeks. It is possible for aunit dosage to contain from about 0.5 mg to about 1500 mg of activeingredient, and can be administered one or more times per day or lessthan once a day. The average daily dosage for administration byinjection, including intravenous, intramuscular, subcutaneous andparenteral injections, and use of infusion techniques will preferably befrom 0.01 to 200 mg/kg of total body weight. The average daily rectaldosage regimen will preferably be from 0.01 to 200 mg/kg of total bodyweight. The average daily vaginal dosage regimen will preferably be from0.01 to 200 mg/kg of total body weight. The average daily topical dosageregimen will preferably be from 0.1 to 200 mg administered between oneto four times daily. The transdermal concentration will preferably bethat required to maintain a daily dose of from 0.01 to 200 mg/kg. Theaverage daily inhalation dosage regimen will preferably be from 0.01 to100 mg/kg of total body weight.

Of course the specific initial and continuing dosage regimen for eachsubject will vary according to the nature and severity of the conditionas determined by the attending diagnostician, the activity of thespecific compound employed, the age and general condition of thesubject, time of administration, route of administration, rate ofexcretion of the drug, drug combinations, and the like. The desired modeof treatment and number of doses of a compound of the present inventionor a pharmaceutically acceptable salt or ester or composition thereofcan be ascertained by those skilled in the art using conventionaltreatment tests.

EXPERIMENTAL SECTION Abbreviations

aq. aqueous DMF dimethylformamide DMSO dimethylsulfoxide MTBEmethyl-t.-butylether THF tetrahydrofurane

The various aspects of the invention described in this application areillustrated by the following examples which are not meant to limit theinvention in any way.

The example testing experiments described herein serve to illustrate thepresent invention and the invention is not limited to the examplesgiven.

Experimental Section—General Part

All reagents, for which the synthesis is not described in theexperimental part, are either commercially available, or are knowncompounds or may be formed from known compounds by known methods by aperson skilled in the art.

The compounds and intermediates produced according to the methods of theinvention may require purification. Purification of organic compounds iswell known to the person skilled in the art and there may be severalways of purifying the same compound. In some cases, no purification maybe necessary. In some cases, the compounds may be purified bycrystallization. In some cases, impurities may be stirred out using asuitable solvent. In some cases, the compounds may be purified bychromatography, particularly flash column chromatography, using forexample prepacked silica gel cartridges, e.g. Biotage SNAP cartidgesKP-Sil® or KP-NH® in combination with a Biotage autopurifier system(SP4® or Isolera Four®) and eluents such as gradients of hexane/ethylacetate or dichloromethane/methanol. In some cases, the compounds may bepurified by preparative HPLC using for example a Waters autopurifierequipped with a diode array detector and/or on-line electrosprayionization mass spectrometer in combination with a suitable prepackedreverse phase column and eluents such as gradients of water andacetonitrile which may contain additives such as trifluoroacetic acid,formic acid or aqueous ammonia.

In some cases, purification methods as described above can provide thosecompounds of the present invention which possess a sufficiently basic oracidic functionality in the form of a salt, such as, in the case of acompound of the present invention which is sufficiently basic, atrifluoroacetate or formate salt for example, or, in the case of acompound of the present invention which is sufficiently acidic, anammonium salt for example. A salt of this type can either be transformedinto its free base or free acid form, respectively, by various methodsknown to the person skilled in the art, or be used as salts insubsequent biological assays. It is to be understood that the specificform (e.g. salt, free base etc.) of a compound of the present inventionas isolated and as described herein is not necessarily the only form inwhich said compound can be applied to a biological assay in order toquantify the specific biological activity.

Analytical and Chromatography Methods

Analytical and Preparative Liquid Chromatography

Analytical (UP)LC-MS was performed by means of different equipments asdescribed below. The masses (m/z) are reported from the positive modeelectrospray ionisation unless the negative mode is indicated (ESI−).

Method L0:

Measurement of log P values was performed according to EEC directive79/831 Annex V.A8 by HPLC (High Performance Liquid Chromatography) onreversed phase columns with the following methods:

-   -   ^([a]) log P value is determined by measurement of LC-UV, in an        acidic range, with 0.1% formic acid in water and acetonitrile as        eluent (linear gradient from 10% acetonitrile to 95%        acetonitrile).    -   ^([b]) log P value is determined by measurement of LC-UV, in a        neutral range, with 0.001 molar ammonium acetate solution in        water and acetonitrile as eluent (linear gradient from 10%        acetonitrile to 95% acetonitrile).

Calibration was done with straight-chain alkan-2-ones (with 3 to 16carbon atoms) with known log P values (measurement of log P values usingretention times with linear interpolation between successive alkanones).Lambda-max-values were determined using UV-spectra from 200 nm to 400 nmand the peak values of the chromatographic signals.

M+1 (or M+H) means the molecular ion peak, plus or minus 1 a.m.u.(atomic mass unit) respectively, as observed in mass spectroscopy byelectrospray ionization (ESI + or −).

Method L1:

Instrument type: Waters ACQUITY SQD UPLC system; column: Waters AcquityUPLC HSS T3 1.8μ 50×1 mm; eluent A: 1 l water+0.25 ml formic acid,eluent B: 1 l acetonitrile+0.25 ml formic acid; gradient: 0.0 min 90%A→1.2 min 5% A→2.0 min 5% A oven: 50° C.; flow: 0.40 ml/min;UV-detection: 208-400 nm.

Method L2:

MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLCinstrument type: Agilent Technologies 1260 Infinity; column: WatersXSelect (C18, 50×2.1 mm, 3.5p); flow: 0.8 mL/min; column temp: 35° C.;eluent A: 0.1% formic acid in acetonitrile; eluent B: 0.1% formic acidin water; lin. gradient: t=0 min 5% A, t=3.5 min 98% A, t=6 min 98% A;detection: DAD (220-320 nm); detection: MSD (ESI pos/neg) mass range:100-800; detection: ELSD (PL-ELS 2100): gas flow 1.2 mL/min, gas temp:70° C., neb: 50° C.

Method L3:

MS instrument type: Agilent Technologies LC/MSD SL; HPLC instrumenttype: Agilent Technologies 1100 Series; column: Waters XSelect (C18,50×2.1 mm, 3.5μ; flow: 0.8 mL/min; column temp: 25° C.; eluent A: 95%acetonitrile+5% 10 mM ammoniumbicarbonate in water;

eluent B: 10 mM ammoniumbicarbonate in water pH=9.0; lin. gradient: t=0min 5% A, t=3.5 min 98% A, t=6 min 98% A; detection: DAD (220-320 nm);detection: MSD (ESI pos/neg) mass range: 100-800.

Method L4:

Instrument type: Waters ACQUITY SQD UPLC System; column: Waters AcquityUPLC HSS T3 1.8μ 50×1 mm; eluent A: 1 l water+0.25 ml 99% ige formicacid, Eluent B: 1 l acetonitrile+0.25 ml 99% ige formic acid; gradient:0.0 min 95% A→6.0 min 5% A→7.5 min 5% A oven: 50° C.; flow: 0.35 ml/min;UV-detection: 210-400 nm.

Method L5:

MS instrument type: Waters SQD; Instrument HPLC: Waters UPLC; column:Zorbax SB-Aq (Agilent), 50 mm×2.1 mm, 1.8 μm; eluent A: water+0.025%formic acid, eluent B: acetonitrile (ULC)+0.025% formic acid; gradient:0.0 min 98% A—0.9 min 25% A—1.0 min 5% A—1.4 min 5% A—1.41 min 98% A—1.5min 98% A; oven: 40° C.; flow: 0.600 ml/min; UV-detection: DAD; 210 nm.

Method L6:

MS instrument type: Thermo Scientific FT-MS; HPLC instrument type:Thermo Scientific UltiMate 3000; column: Waters, HSST3, 2.1×75 mm, C181.8 μm; eluent A: 1 l water+0.01% formic acid; eluent B: 1 lacetonitril+0.01% formic acid; Gradient: 0.0 min 10% B→2.5 min 95% B→3.5min 95% B; Ofen: 50° C.; Fluss: 0.90 ml/min; UV-Detektion: 210nm/optimum integration path 210-300 nm:

Method L7:

MS instrument type: Waters (Micromass) Quattro Micro; HPLC instrumenttype: Waters UPLC Acquity; column: Waters BEH C18 1.7μ 50×2.1 mm; eluentA: 1 l water+0.01 mol ammoniumformiate, eluent B: 1 l acetonitril;gradient: 0.0 min 95% A→0.1 min 95% A→2.0 min 15% A→2.5 min 15% A→2.51min 10% A→3.0 min 10% A; oven: 40° C.; flow: 0.5 ml/min; UV-detection:210 nm.

Method L8:

MS instrument type: Waters SQD2; Instrument HPLC: Waters UPLC; column:Zorbax SB-Aq (Agilent), 50 mm×2.1 mm, 1.8 μm; eluent A: water+0.025%formic acid, eluent B: acetonitrile (ULC)+0.025% formic acid; gradient:0.0 min 98% A—0.9 min 25% A—1.0 min 5% A—1.4 min 5% A—1.41 min 98% A—1.5min 98% A; oven: 40° C.; flow: 0.600 ml/min; UV-detection: DAD; 210 nm.

Method L9:

MS instrument type: Agilent Technologies LC/MSD SL; HPLC instrumenttype: Agilent Technologies 1100 Series; column: Waters XSelect (C18,50×2.1 mm, 3.5μ; flow: 0.8 mL/min; column temp: 25° C.; eluent A: 95%acetonitrile+5% ammoniumbicarbonate in water; eluent B: 10 mmMammoniumbicarbonate in water pH=9.0; lin. gradient: t=0 min 5% A, t=3.5min 98% A, t=6 min 98% A; detection: DAD (220-320 nm); detection: MSD(ESI pos/neg) mass range: 100-800.

Method L10:

MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLCinstrument type: Agilent Technologies 1260 Infinity; column: WatersXSelect (C18, 30×2.1 mm, 3.5p); flow: 1 mL/min; column temp: 35° C.;eluent A: 0.1% formic acid in acetonitrile; eluent B: 0.1% formic acidin water; lin. gradient: t=0 min 5% A, t=1.6 min 98% A, t=3 min 98% A;detection: DAD (220-320 nm); detection: MSD (ESI pos/neg) mass range:100-800; detection: ELSD (PL-ELS 2100): gas flow 1.2 mL/min, gas temp:70° C., neb: 50° C.

Method L11:

MS instrument type: Agilent Technologies LC/MSD SL; HPLC instrumenttype: Agilent Technologies 1100 Series; column: Phenomenex Gemini NX(C18, 50×2.0 mm), 3.0μ; flow: 0.8 mL/min; column temp: 25° C.; eluent A:95% acetonitrile+5% 10 mM ammoniumbicarbonate in water in acetonitrilepH=9.0; eluent B: 10 mM ammoniumbicarbonate in water pH=9.0; lin.gradient: t=0 min 5% A, t=3.5 min 98% A, t=6 min 98% A; detection: DAD(220-320 nm); detection: MSD (ESI pos/neg) mass range: 100-800.

Method L12:

MA instrument: Agilent MS Quad 6150; HPLC instrument: Agilent 1290;column: Waters Acquity UPLC HSS T3 1.8 μm 50×2.1 mm; eluent A: 1 lwater+0.25 ml 99% formic acid, Eluent B: 1 l acetonitril+0.25 ml 99%formic acid; gradient: 0.0 min 90% A→0.3 min 90% A→1.7 min 5% A→3.0 min5% A oven: 50° C.; flow: 1.20 ml/min; UV-detection: 205-305 nm.

Method M1:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 1.80 min with a total runtime of 2.10 min. The column temperature was at 45° C. with the flowrate of 1.20 mL/min.

Method M2:

The column used was an EVO, 2.6 μm, 3.0×50 mm. A linear gradient wasapplied, starting at 90% A (A: 0.1% FA in water) and ending at 95% B (B:0.1% FA in MeCN) over 4.20 min with a total run time of 4.50 min. Thecolumn temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M3:

The column used was a CORTECS C18, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 95% A (A: 0.09% FA in water) and ending at 100%B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of 2.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M4:

The column used was a CORTECS C18+, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 90% A (A: 0.1% FA in water) and ending at 100%B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of 2.00 min.The column temperature was at 45° C. with the flow rate of 1.00 mL/min.

Method M5:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.1% FA in water) and endingat 100% B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of2.00 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M6:

The column used was a CORTECS C18, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 95% A (A: 0.09% FA in water) and ending at 100%B (B: 0.1% FA in MeCN) over 2.60 min with a total run time of 3.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M7:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 2.80 min with a total runtime of 3.30 min. The column temperature was at 45° C. with the flowrate of 1.20 mL/min.

Method M8:

The column used was a CORTECS C18+, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 90% A (A: 0.1% FA in water) and ending at 100%B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of 2.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M9:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.1% FA in water) and endingat 95% B (B: 0.1% FA in MeCN) over 4.20 min with a total run time of4.50 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M10:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.1% FA in water) and endingat 100% B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of2.00 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M11:

The column used was a CORTECS C18+, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 90% A (A: 0.1% FA in water) and ending at 95% B(B: 0.1% FA in MeCN) over 2.70 min with a total run time of 3.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M12:

The column used was an Ascentis Express C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.09% FA in water) andending at 100% B (B: 0.1% FA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.50 mL/min.

Method M13:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M14:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 2.70 min with a total runtime of 3.00 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M15:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 70% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 2.70 min with a total runtime of 3.00 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M16:

The column used was a CORTECS C18, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 95% A (A: 0.09% FA in water) and ending at 100%B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of 2.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M17:

The column used was a CORTECS C18+100A, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 90% A (A: 0.1% FA in water) and endingat 100% B (B: 0.1% FA in MeCN) over 1.60 min with a total run time of2.00 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M18:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.09% FA in water) andending at 100% B (B: 0.1% FA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M19:

The column used was a Kinetex EVO C18 100A, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.1% FA in water) and endingat 100% B (B: 0.1% FA in MeCN) over 1.60 min with a total run time of2.00 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M20:

The column used was an Ascentis Express C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.50 mL/min.

Method M21:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.09% FA in water) andending at 100% B (B: 0.1% FA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.50 mL/min.

Method M22:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.09% FA in water) andending at 95% B (B: 0.1% FA in MeCN) over 2.70 min with a total run timeof 3.00 min. The column temperature was at 40° C. with the flow rate of1.50 mL/min.

Method M23:

The column used was an Ascentis Express C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 0.09% FA in water) andending at 95% B (B: 0.1% FA in MeCN) over 2.70 min with a total run timeof 3.00 min. The column temperature was at 40° C. with the flow rate of1.50 mL/min.

Method M24:

The column used was an Ascentis Express C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 2.70 min with a total runtime of 3.00 min. The column temperature was at 40° C. with the flowrate of 1.50 mL/min.

Method M25:

The column used was a Kinetex EVO C18, 2.6 μm, 4.6×50 mm. A lineargradient was applied, starting at 90% A (A: 5mMNH₄HCO₃ in water) andending at 95% B (B: MeCN) over 1.75 min with a total run time of 2.00min. The column temperature was at 40° C. with the flow rate of 1.80mL/min.

Method M26:

The column used was an Ascentis Express C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 4.90 min with a total runtime of 5.30 min. The column temperature was at 45° C. with the flowrate of 1.50 mL/min.

Method M27:

The column used was an Poroshell HPH-C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.1% FA in water) and endingat 100% B (B: 0.1% FA in MeCN) over 1.70 min with a total run time of2.00 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M28:

The column used was a CORTECS C18+, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 90% A (A: 0.1% FA in water) and ending at 95% B(B: 0.1% FA in MeCN) over 2.70 min with a total run time of 3.00 min.The column temperature was at 45° C. with the flow rate of 1.00 mL/min.

Method M29:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 4.60 min with a total runtime of 5.30 min. The column temperature was at 40° C. with the flowrate of 1.20 mL/min.

Method M30:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 2.80 min with a total runtime of 3.30 min. The column temperature was at 45° C. with the flowrate of 1.20 mL/min.

Method M31:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 4.70 min with a total runtime of 5.00 min. The column temperature was at 45° C. with the flowrate of 1.20 mL/min.

Method M32:

The column used was a CORTECS C18+, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 90% A (A: 0.1% FA in water) and ending at 95% B(B: 0.1% FA in MeCN) over 5.20 min with a total run time of 5.70 min.The column temperature was at 45° C. with the flow rate of 1.00 mL/min.

Method M33:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 2.20 min with a total runtime of 2.60 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M34:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.20 mL/min.

Method M35:

The column used was a CORTECS C18+, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 95% A (A: 0.09% FA in water) and ending at 95%B (B: 0.1% FA in MeCN) over 2.70 min with a total run time of 3.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M36:

The column used was a CORTECS C18+100A, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 90% A (A: 0.1% FA in water) and endingat 100% B (B: 0.1% FA in MeCN) over 2.60 min with a total run time of3.00 min. The column temperature was at 40° C. with the flow rate of1.00 mL/min.

Method M37:

The column used was a CORTECS C18, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 95% A (A: 0.09% FA in water) and ending at 95%B (B: 0.1% FA in MeCN) over 2.60 min with a total run time of 3.00 min.The column temperature was at 40° C. with the flow rate of 1.00 mL/min.

Method M38:

The column used was a CORTECS C18, 2.7 μm, 2.1×50 mm. A linear gradientwas applied, starting at 95% A (A: 0.05% TFA in water) and ending at100% B (B: 0.05% TFA in MeCN) over 1.80 min with a total run time of2.00 min. The column temperature was at 45° C. with the flow rate of1.00 mL/min.

Method M39:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 70% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 5.70 min with a total runtime of 6.50 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M40:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 60% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 2.70 min with a total runtime of 3.00 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M41:

The column used was a Kinetex EVO C18, 2.6 μm, 3.0×50 mm. A lineargradient was applied, starting at 90% A (A: 5 mM NH₄HCO₃ in water) andending at 95% B (B: MeCN) over 1.80 min with a total run time of 2.00min. The column temperature was at 45° C. with the flow rate of 1.50mL/min.

Method M42:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 1.70 min with a total runtime of 2.00 min. The column temperature was at 40° C. with the flowrate of 1.20 mL/min.

Method M43:

The column used was a Kinetex EVO C18 100A, 2.6 μm, 2.1×50 mm. A lineargradient was applied, starting at 90% A (A: 5 mM NH₄HCO₃ in water) andending at 95% B (B: MeCN) over 2.60 min with a total run time of 3.00min. The column temperature was at 40° C. with the flow rate of 1.00mL/min.

Method M44:

The column used was a HPH-C18, 2.7 μm, 3.0×50 mm. A linear gradient wasapplied, starting at 90% A (A: 5 mM NH₄HCO₃ in water) and ending at 100%B (B: MeCN) over 2.60 min with a total run time of 3.00 min. The columntemperature was at 40° C. with the flow rate of 1.50 mL/min.

Method 45:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 3.10 min with a total runtime of 3.60 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M46:

The column used was an Ascentis Express C18, 2.7 μm, 2.1×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 100% B (B: 0.05% TFA in MeCN) over 2.10 min with a total runtime of 2.60 min. The column temperature was at 40° C. with the flowrate of 1.00 mL/min.

Method M47:

The column used was an Ascentis Express C18, 2.7 μm, 3.0×50 mm. A lineargradient was applied, starting at 95% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 4.20 min with a total runtime of 4.50 min. The column temperature was at 40° C. with the flowrate of 1.50 mL/min.

Method M48:

The column used was a Shim-pack XR-ODS, 2.2 μm, 3.0×50 mm. A lineargradient was applied, starting at 80% A (A: 0.05% TFA in water) andending at 95% B (B: 0.05% TFA in MeCN) over 5.00 min with a total runtime of 5.60 min. The column temperature was at 45° C. with the flowrate of 1.20 mL/min.

¹H-NMR Data

¹H-NMR data were determined with a Bruker Avance 400 (equipped with aflow cell (60 μl volume), or with a Bruker AVIII 400 equipped with 1.7mm cryo CPTCI probe head, or with a Bruker AVIII 400 (400.13 MHz)equipped with a 5 mm probe head, or with a Bruker AVII 600 (600.13 MHz)equipped with a 5 mm cryo TCI probe head, or with a Bruker AVIII 600(601.6 MHz) equipped with a 5 mm cryo CPMNP probe head, or with a BrukerAVIII 500 (500.13 MHz) equipped with a 5 mm broadband head or a 5 mmProdigy™ probe head, with tetramethylsilane as reference (0.0) and thesolvents CD₃CN, CDCl₃ or D₆-DMSO. Alternative ¹H- and ¹³C-NMR instrumenttypes: Bruker DMX300 (¹H-NMR: 300 MHz; ¹³C NMR: 75 MHz), Bruker AvanceIII 400 (¹H-NMR: 400 MHz; ¹³C NMR: 100 MHz) or Bruker 400 Ultrashield(¹H-NMR: 400 MHz; ¹³C NMR: 100 MHz).

Chemical shifts (δ) are displayed in parts per million [ppm]; thefollowing abbreviations are used: s=singlet, d=doublet, t=triplet,q=quartet, m=multiplet, br.=broad; coupling constants are displayed inHertz [Hz].

Experimental Section—General Procedures

The synthesis of the compounds of the formula (I) can be performedaccording to or in analogy to the following schemes (Scheme 1a-e, Scheme2 and Scheme 3).

2-Halogen-substituted anilines 1A (Hal=iodine, bromine, chlorine) arecommercial available and can be readily converted with(alkoxymethylen)malonates 1B dissolved the corresponding alcoholsolvent, preferably under boiling conditions into(anilinomethylene)malonates 1C as described in Monatshefte fuer Chemie,2015, 146(2), 291-302 or without any solvent as described in WO2002004444. The ring closure is performed in high boiling solvents,preferably in diphenylether or xylol, to achieve hydroxy quinolines 1Das described in WO 2013118071. The hydroxy quinolines 1D can be easilyconverted into the corresponding chlorine compounds 1E with achlorination reagent, preferably refluxing POCl₃ as described in WO2013118071.

Depended on the nature of the nucleophile R²H 1F, the chloro quinolines1E reacts with 1F in the presence of a base, e.g. sodium ethylate,sodium methylate, potassium t-butylate, triethylamine N,N-diisopropylethylamine, diazabicycloundecan, sodium hydride, lithium hydroxide,sodium hydroxide, potassium hydroxide, potassium carbonate, cesiumcarbonate, or the like to obtain ester intermediates 1G.

Alternatively, a Suzuki cross coupling reaction of intermediates 1D withboronic acids or boronic esters 1H Q-B(OR)₂ (R═H; R=Me orR,R=pinacolate) as described in Chem. Soc. Rev. 2014, 43, 412-443 or inTetrahedron 2002, 58 (48), 9633-9695 to ester intermediates 11.Subsequently, the ester intermediates 11 can be smoothly saponified e.g.with lithium hydroxide resulting in the corresponding carboxylic acids1J, which can be easily converted into the corresponding chlorocarboxylic chlorides 1K with a chlorination reagent, preferablyrefluxing POCl₃ as described in WO 2013096151. Intermediates 1K reactunder hydrolytic conditions to yield quinolone carboxylic acids 1L,which are combined with commercial available amines 1M via an amideformation and dehydration reagents, e.g.N-(3-di-methylaminoisopropyl)-N′-ethylcarbodiimide-hydrochloride (EDC)to give amides 1N. Similar syntheses are described in Journal ofMedicinal Chemistry 2012, 55, 3563-3567 for example. Intermediates 1Kcan directly form the amides 1N as the carboxylic acid chlorides 1K arecombined with amines 1M under basic conditions, e.g. pyridine,triethylamine or N,N-diisopropyl ethylamine as described in ChemicalBiology & Drug Design 2015, 85(5), 549-564. Depended on the nature ofthe nucleophile R²H 1F, the chloro quinolines 1N reacts with 1F in thepresence of a base, e.g. sodium ethylate, sodium methylate, potassiumt-butylate, triethylamine N,N-diisopropyl ethylamine,diazabicycloundecan, sodium hydride, lithium hydroxide, sodiumhydroxide, potassium hydroxide, potassium carbonate, cesium carbonate,or the like to obtain the target compounds of formula (I).

Chloro quinolines 1E can be smoothly saponified e.g. with lithiumhydroxide resulting in the corresponding carboxylates 1O, obtained e.g.as lithium salt, or resulting in the carboxylic acids 1P after acidhydrolysis. Subsequently, the intermediate carboxamides 1S are obtainedby amide coupling conditions, e.g. via carboxylic acid chlorides formedfrom 1P which are combined with amines 1M under basic conditions, e.g.pyridine, triethylamine or N,N-diisopropyl ethylamine or via amideformation from the carboxylic acids 1P which are combined with amines 1Mand dehydration reagents, e.g.N-(3-dimethylaminoisopropyl)-N′-ethylcarbodiimide-hydrochloride (EDC).Similar syntheses are described in Journal of Medicinal Chemistry 2012,55, 3563-3567 for example. Dependend on the nature of the nucleophileR²H 1F, the chloro quinolines 1S react with 1F in the presence of abase, e.g. sodium ethylate, sodium methylate, potassium t-butylate,triethylamine N,N-diisopropyl ethylamine, diazabicycloundecan, sodiumhydride, lithium hydroxide, sodium hydroxide, potassium hydroxide,potassium carbonate, cesium carbonate, or the like to obtain theintermediate carboxamides 1T. A Suzuki cross coupling reaction ofintermediate carboxamides 1T with boronic acids or boronic esters 1HQ-B(OR)2 (R═H; R=Me or R,R=pinacolate) as described in Chem. Soc. Rev.2014, 43, 412-443 or in Tetrahedron 2002, 58 (48), 9633-9695 leads tothe final products of formula (I).

Alternatively, chloro quinolines 1E react via a Suzuki cross couplingreaction with boronic acids or boronic esters 1H Q-B(OR)2 (R═H; R=Me orR,R=pinacolate) as described in Chem. Soc. Rev. 2014, 43, 412-443 or inTetrahedron 2002, 58 (48), 9633-9695 to provide quinoline carboxylicesters 1Q, which can be smoothly saponified e.g. with lithium hydroxideresulting in the corresponding quinoline carboxylic acid 1R.Subsequently, the intermediate carboxamides 1N are obtained by amidecoupling conditions, e.g. via carboxylic acid chlorides formed from 1Rwhich are combined with amines 1M under basic conditions, e.g. pyridine,triethylamine or N,N-diisopropyl ethylamine or via amide formation fromthe carboxylic acids 1R which are combined with amines 1M anddehydration reagents, e.g.N-(3-dimethylaminoisopropyl)-N′-ethylcarbodiimide-hydrochloride (EDC).Similar syntheses are described in Journal of Medicinal Chemistry 2012,55, 3563-3567 for example. Dependend on the nature of the nucleophileR²H 1F, the chloro quinolines 1N react with 1F in the presence of abase, e.g. sodium ethylate, sodium methylate, potassium t-butylate,triethylamine N,N-diisopropyl ethylamine, diazabicycloundecan, sodiumhydride, lithium hydroxide, sodium hydroxide, potassium hydroxide,potassium carbonate, cesium carbonate, or the like to obtain the thefinal products of formula (I) as well.

Quinoline carboxylic esters 1G can be converted via a Suzuki crosscoupling reaction with boronic acids or boronic esters 1H Q-B(OR)2 (R═H;R=Me or R,R=pinacolate) as described in Chem. Soc. Rev. 2014, 43,412-443 or in Tetrahedron 2002, 58 (48), 9633-9695 to provide quinolinecarboxylic esters 1U, which can be smoothly saponified e.g. with lithiumhydroxide resulting in the corresponding quinoline carboxylic acid 1W.Subsequently, the final products of formula (I) are obtained by amidecoupling conditions, e.g. via carboxylic acid chlorides formed from 1Wwhich are combined with amines 1M under basic conditions, e.g. pyridine,triethylamine or N,N-diisopropyl ethylamine or via amide formation fromthe carboxylic acids 1W which are combined with amines 1M anddehydration reagents, e.g.N-(3-dimethylamino-isopropyl)-N′-ethylcarbodiimide-hydrochloride (EDC).Similar syntheses are described in Journal of Medicinal Chemistry 2012,55, 3563-3567 for example.

Alternatively, quinoline carboxylic esters 1G can be saponified firstand then converted via a Suzuki cross coupling reaction with boronicacids or boronic esters 1H Q-B(OR)2 (R═H; R=Me or R,R=pinacolate) intoquinoline carboxylic acids 1W or transformed into quinoline carboxamides1T by means of amide coupling conditions, e.g. via quinoline carboxylicacid chlorides formed from 1V which are combined with amines 1M underbasic conditions, e.g. pyridine, triethylamine or N,N-diisopropylethylamine or via amide formation from the quinolone carboxylic acids 1Vwhich are combined with amines 1M and dehydration reagents, e.g.N-(3-dimethylaminoisopropyl)-N′-ethylcarbodiimide-hydrochloride (EDC).Finally, quinoline carboxamides 1T can be converted via a Suzuki crosscoupling reaction with boronic acids or boronic esters 1H Q-B(OR)2 (R═H;R=Me or R,R=pinacolate) as described in Chem. Soc. Rev. 2014, 43,412-443 or in Tetrahedron 2002, 58 (48), 9633-9695 into final productsof formula (I).

A subgroup of 1G, where R² is an alkyl group, such as methyl (R₃₀═H) canbe halogenated, e.g. brominated by brominating agents such as bromine,N-bromo-succinimide, pyridinium tribromide or phenyltrimethylammoniumtribromide to bromoalkylderivatives 1G′ as described e.g. in J.Heterocl. Chem. 1981, vol. 18, 925-928, J. Med. Chem., 2009, vol. 52,3047-3062 or J. Am. Chem. Soc., 1948, 70, 417-418. Such bromoalkylcompounds 1G′ can be substituted by nucleophiles such as amines,alkohols or thiols or their salts, occasionally in presence of baseaccording to standard procedures to furnish substituted alkyl-quinolines1G″. Under the reaction conditions of the nucleophilic substitution theesters 1G″ can be further converted to the corresponding acids 1V″ orthey can be isolated and converted in a separate hydrolysis step to theacids 1V″. Then, the final products (I) can be obtained from the acids1V″ by amide formation and coupling of the group Q by the methodsdescribed in scheme 1d.

Hydroxy quinolones 1X are obtained by amide coupling conditions, e.g.via carboxylic acid chlorides formed from 1J which are combined withamines 1M under basic conditions, e.g. pyridine, triethylamine orN,N-diisopropyl ethylamine or via amide formation from the carboxylicacids 1J which are combined with amines 1M and dehydration reagents,e.g. N-(3-di-methylaminoisopropyl)-N′-ethylcarbodiimide-hydrochloride(EDC). Similar syntheses are described in Journal of Medicinal Chemistry2012, 55, 3563-3567 for example. The final products of formula (I) areobtained by a Mitsunobu reaction of hydroxy quinolones 1X with alcohols1Y (R²═C₁-C₄-alkoxy, optionally substituted) in the presence ofdehydrating reagents, e.g. diisopropyl-(E)-diazene-1,2-dicarboxylate andtriphenylphosphine as described in Organic & Biomolecular Chemistry2012, 10(32), 6537-6546.

Quinoline carboxylic ester intermediates 1Q or quinolone carboxamideintermediates 1N can be converted with certain Grignard- or metalorganic compounds 2A: C₁-C₄-alkyl-Met-X, C₃-C₆-cycloalkyl-Met-X,C₂-C₄-alkenyl-Met-X, C₃-C₆-cycloalkenyl-Met-X, C₂-C₄-alkynyl-Met-X orphenyl-C₁-C₄-alkyl-Met-X (Met=Mg, Zn; X═I, Br, Cl) introducingC₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl,C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, each of which is optionallysubstituted as defined for the compound of general formula (I) asdefined supra, as described in Tetrahedron Letters, 2000, 41(33),6387-6391 for example, into ester intermediates 2B or final compoundsI-a.

An alternative route to obtain hydroxyl ester 3C(R³═C₁-C₄-alkyl,R^(A)=methyl, ethyl or t.-butyl) uses commercial available2H-3,1-oxazine-2,4(1H)-diones 3A (Hal=iodine, bromine, chlorine) in adecarboxylation reaction with ketoesters 3B (R³═C₁-C₄-alkyl,R^(A)=methyl, ethyl or t.-butyl) in the presence of a base, e.g. sodiumhydride in polar high boiling solvents, e.g. N,N-dimethyl acetamide asdescribed in US 20080306048. The following steps can be performedaccording to Scheme 1a-e or Scheme 2.

Quinolone carboxamide intermediates 1N can be converted by photoredoxcatalysis with certain alkyl, clycloalkyl and hetercyclooalkyl halidesor carboxylic acids 3A: C₁-C₄-alkyl-X, C₃-C₆-cycloalkyl-X,C₃-C₆-cycloalkenyl-X, heterocycloalkyl-X (X═Br, COOH) introducingC₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, heterocycloalkyl eachof which is optionally substituted as defined for the compound ofgeneral formula (I) as defined supra, as described in J. Org. Chem.,2016, 81 (16), pp 6898-6926 or Chem. Rev., 2013, 113 (7), pp 5322-5363.

EXPERIMENTAL SECTION—EXAMPLES Synthesis of8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(R²)quinoline-3-carboxamides(examples 135, 137, 150, 188, 189, 243, 261, 264, 273)

Step 1

8-(3,5-dichlorophenyl)-4-hydroxyquinoline-3-carboxylic acid

Under argon atmosphere a flask was charged with ethyl8-bromo-4-hydroxy-quinoline-3-carboxylate (15.0 g, 50.7 mmol) (Gharat,al., WO 2013/118071), 3,5-dichlorobenzene boronic acid (11.6 g, 60.8mmol), potassium carbonate (14.0 g, 101 mmol)1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (1.24 g, 1.52 mmol) and a degassed 5:1 mixtureof dioxan and water (190 ml). The suspension was stirred overnight at70° C. Then an aqueous solution of sodium hydroxide (5 M, 101 ml, 505mmol) was added and the dark mixture was refluxed for 6 h. Subsequently,hot water (110 ml), methanol (70 ml) and charcoal (2.5 g) were added andrefluxing continued for a few minutes. The mixture was filtered hot andthe filter cake washed with methanol/water (1:1). 5 M acetic acid (150ml, 750 mmol) was added slowly under stirring to the hot filtrate toachieve a pH range of 6-7. Further 90 ml of water were added and thesolvents were partially removed under reduced pressure. The suspensionwas cooled under stirring to RT and lateron to 0° C. The precipitate wasfiltered off, washed with methanol/water (2:1), stirred in MTBE,filtered off again and dried in vacuo.

Yield: 17.5 g (92% purity, 95% of th.)

LC-MS (Method L1): R_(f)=1.02 min; MS (ESIpos): m/z=334 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (1.06), 0.008 (0.98),1.909 (9.53), 2.524 (1.24), 2.670 (0.41), 3.162 (0.87), 3.175 (0.89),3.568 (5.51), 7.609 (2.04), 7.628 (3.44), 7.650 (15.61), 7.654 (16.00),7.769 (2.83), 7.773 (4.62), 7.778 (2.66), 7.788 (3.38), 7.791 (3.46),7.806 (2.84), 7.809 (2.66), 7.874 (0.44), 7.879 (0.42), 7.948 (0.51),7.952 (0.48), 8.364 (3.52), 8.368 (3.54), 8.385 (3.50), 8.388 (3.26),8.603 (10.14), 12.202 (1.00).

Step 2

4-chloro-8-(3,5-dichlorophenyl)quinoline-3-carbonyl chloride

To a suspension of8-(3,5-dichlorophenyl)-4-hydroxyquinoline-3-carboxylic acid (step 1)(8.10 g, 24.2 mmol) in chloroform (48 ml) under stirring were added DMF(4 drops) and oxalylchloride (40 ml, 460 mmol) slowly during 1 h atambient temperature, causing significant gas evolution. Then, themixture was slowly heated to reflux and stirred at reflux temperaturefor 3.5 h. The volatiles were evaporated under reduced pressure and theresidue was co-evaporated twice with dry dichloromethane and once withdry THF. The crude product (9.0 g, 100%) was used in the next step.

¹H-NMR (400 MHz, CHLOROFORM-d): δ [ppm]=9.42 (s, 1H), 8.53 (dd, 1H),7.89-7.95 (m, 1H), 7.80-7.87 (m, 1H), 7.53 (d, 2H), 7.46 (t, 1H).

Step 3

4-chloro-8-(3,5-dichlorophenyl)quinoline-3-carboxylic acid

4-chloro-8-(3,5-dichlorophenyl)quinoline-3-carbonyl chloride (step 2)(5.40 g, 14.6 mmol) was suspended in THF (100 ml). Water (25 ml) andsodium hydrogencarbonate (2.0 g, 23.8 mmol) were added until a pH 5 ismaintained and the reaction mixture was stirred overnight at ambienttemperature. The THF was largely removed under reduced pressure at abath temperature not exceeding 40° C. Acetonitril (20 ml) was added andthe organic solvents were removed again under reduced pressure. Thisprocedure was repeated and the suspension was cooled to 0° C. Theprecipitate was filtered off, washed with little volumes ofacetonitrile/water (2:1) and petrolether and dried in vacuo.

Yield: 5.10 g (93% purity, 92% of th.)

LC-MS (Method L1): R_(f)=1.16 min; MS (ESIpos): m/z=352 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (1.29), 0.008 (1.20),1.760 (0.44), 2.329 (0.64), 2.367 (0.44), 2.524 (2.38), 2.671 (0.63),2.711 (0.43), 3.601 (0.50), 7.654 (1.72), 7.660 (4.30), 7.664 (6.77),7.669 (16.00), 7.673 (7.64), 7.804 (1.91), 7.823 (3.49), 7.843 (3.22),7.887 (3.53), 7.890 (3.71), 7.904 (2.79), 8.354 (3.04), 8.357 (3.11),8.375 (2.85), 8.378 (2.73), 8.907 (6.32).

Step 4a

4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(Example 4)

To a solution of 4-chloro-8-(3,5-dichlorophenyl)quinoline-3-carboxylicacid (step 3) (7.60 g, 21.6 mmol) in THF (110 ml) were added understirring (4S)-chroman-4-amine hydrochloride (4.4 g, 23.7 mmol),triethylamine (12 ml, 86 mmol) and after 10 min at ambient temperature asolution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane2,4,6-trioxide in ethylacetate (19 ml, 50 content, 32 mmol), whereafterthe temperature of the mixture was raised to 36° C. After stirringovernight at ambient temperature further (4S)-chroman-4-aminehydrochloride (0.8 g, 4.3 mmol), triethylamine (3 ml, 21.5 mmol) and asolution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane2,4,6-trioxide in ethylacetate (3.85 ml, 50% content, 6.5 mmol) wereadded and stirring continued at ambient temperature for another night.Then water was added and most of the organic solvents evaporated underreduced pressure. The formed precipitate was filtered off and washedwith petrolether and was dried in vacuo.

Yield: 10.0 g (94% purity, 90% of th.)

LC-MS (Method L1): R_(f)=1.35 min; MS (ESIpos): m/z=483 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 1.356 (1.31), 1.743 (2.45),1.752 (3.18), 1.759 (6.79), 1.768 (3.21), 1.776 (2.57), 1.988 (0.51),2.059 (0.99), 2.066 (1.07), 2.076 (1.22), 2.084 (1.26), 2.093 (1.57),2.100 (1.38), 2.209 (1.45), 2.221 (1.33), 2.229 (1.27), 2.242 (0.90),2.366 (0.47), 3.585 (2.47), 3.601 (5.93), 3.617 (2.49), 4.221 (0.89),4.241 (2.24), 4.249 (1.82), 4.262 (2.18), 4.270 (2.80), 4.279 (2.21),4.287 (1.82), 4.296 (1.93), 4.315 (0.75), 5.267 (0.91), 5.282 (2.01),5.301 (2.05), 5.315 (0.88), 6.791 (3.63), 6.811 (4.03), 6.917 (1.84),6.936 (3.82), 6.955 (2.20), 7.161 (2.03), 7.179 (3.22), 7.199 (1.53),7.380 (3.39), 7.399 (3.19), 7.680 (16.00), 7.879 (0.46), 7.893 (2.16),7.912 (3.99), 7.932 (3.43), 8.009 (4.26), 8.026 (2.94), 8.389 (3.75),8.410 (3.33), 8.962 (9.97), 9.251 (3.23), 9.272 (3.16).

Step 4b

4-chloro-8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]quinoline-3-carboxamide(Example 3)

To a stirred mixture of4-chloro-8-(3,5-dichlorophenyl)quinoline-3-carbonyl chloride (step 2)(480 mg, 1.29 mmol) in DMF (4 ml) was added triethylamine (0.36 ml, 2.6mmol) and then dropwise a solution of (1S)-indan-1-amine (0.18 ml, 2.6mmol) in dichloromethane (1.2 ml) at 0° C. The reaction mixture wasstirred 1 h at 0° C., then warmed to ambient temperature and the pHadjusted to 5-6 with 1 M acetic acid followed by addition of water andextraction with dichloromethane. The organic phases were separated andevaporated under reduced pressure and the residue was purified by columnchromatography on silica (100 g), eluent: cyclohexane/ethyl acetate(9-40%).

Yield: 149 mg (25% of th.)

LC-MS (Method L1): R_(f)=1.37 min; MS (ESIpos): m/z=467 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 0.008 (1.33), 1.234 (2.20),1.397 (0.85), 1.924 (1.63), 1.935 (0.83), 1.946 (1.76), 1.956 (1.90),1.967 (0.79), 1.977 (1.84), 1.998 (0.66), 2.524 (2.18), 2.567 (0.88),2.575 (0.77), 2.838 (0.77), 2.859 (1.28), 2.878 (2.28), 2.898 (2.50),2.918 (1.19), 2.951 (1.54), 2.959 (1.64), 2.973 (1.71), 2.980 (1.81),2.990 (0.99), 2.999 (0.88), 3.012 (0.86), 3.020 (0.74), 3.070 (1.91),5.542 (1.02), 5.562 (2.83), 5.582 (2.79), 5.602 (0.92), 7.223 (0.96),7.232 (4.00), 7.240 (4.95), 7.246 (5.24), 7.254 (7.15), 7.263 (2.96),7.271 (3.67), 7.281 (2.50), 7.293 (1.17), 7.435 (2.55), 7.446 (2.61),7.456 (2.00), 7.635 (1.10), 7.665 (0.98), 7.678 (13.08), 7.681 (16.00),7.686 (7.10), 7.689 (3.73), 7.695 (1.37), 7.700 (0.80), 7.895 (2.06),7.913 (4.25), 7.934 (3.06), 8.004 (4.66), 8.008 (3.27), 8.022 (3.28),8.026 (2.07), 8.393 (4.14), 8.396 (2.75), 8.414 (3.73), 8.417 (2.39),8.962 (10.00), 9.118 (3.31), 9.139 (3.23).

Step 5

4-(azetidin-1-yl)-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(Example 135)

In a thick-walled microwave vessel triethylamine (84 μl, 0.6 mmol) andazetidine (40 μl, 0.6 mmol) were added to a solution of4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4a) (145 mg, 0.3 mmol) in N-methyl pyrrolidon. The vessel wascapped and heated under stirring to 100° C. for 2.5 h. 5 M formic acid(180 μl, 0.9 mmol) and little DMSO were added to the dark mixture andthe solution purified by prep. HPLC (C18, gradient: 0.1% aq. formicacid/acetonitrile).

Yield: 93 mg (62% of th.)

LC-MS (Method L1): R_(f)=0.89 min; MS (ESIpos): m/z=504 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (6.30), 0.008 (2.98),2.004 (1.02), 2.014 (0.94), 2.026 (1.43), 2.041 (1.28), 2.126 (1.31),2.141 (1.56), 2.373 (2.15), 2.394 (2.92), 2.412 (2.16), 2.433 (1.25),2.519 (4.80), 2.523 (4.67), 4.243 (3.28), 4.255 (4.75), 4.261 (3.01),4.270 (2.58), 4.427 (5.50), 4.446 (8.06), 4.466 (4.62), 5.160 (0.92),5.174 (1.75), 5.194 (1.64), 5.754 (2.42), 6.781 (3.04), 6.785 (3.14),6.802 (3.39), 6.805 (3.26), 6.887 (1.73), 6.890 (1.66), 6.906 (3.30),6.909 (2.99), 6.924 (1.93), 6.927 (1.70), 7.142 (1.75), 7.146 (1.77),7.163 (2.63), 7.180 (1.31), 7.185 (1.20), 7.291 (2.83), 7.311 (2.52),7.434 (2.40), 7.452 (3.13), 7.455 (2.90), 7.473 (2.61), 7.592 (2.65),7.597 (4.87), 7.602 (5.82), 7.611 (16.00), 7.616 (8.48), 7.698 (3.62),7.701 (3.63), 7.716 (3.07), 7.719 (2.82), 8.058 (3.06), 8.061 (3.05),8.080 (2.76), 8.083 (2.47), 8.430 (11.34), 8.946 (2.94), 8.966 (2.74).

ethylN-{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}-N-methylglycinate(Example 137)

Under argon atmosphere a thick-walled microwave vessel was charged with1,4-diazabicyclo(2.2.2)octane (56 mg, 0.5 mmol),ethyl-N-methylglycinatehydrochloride (1:1) (154 mg, 1.0 mmol),N,N-diisopropylethylamine (350 μl, 2.0 mmol), N-methyl pyrrolidon (0.8ml) and4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4a) (242 mg, 0.5 mmol). The vessel was capped and the mixtureheated under stirring at 100° C. for 3 h. Further amounts ofethyl-N-methylglycinatehydrochloride (1:1) (77 mg, 0.5 mmol),N,N-diisopropylethylamine (170 μl, 1.0 mmol) were added and heatingcontinued for 2 h. 5 M formic acid (0.7 ml, 3.5 mmol) and DMSO (3 ml)were added and the solution purified by prep. HPLC (C18, gradient: 0.1%aq. formic acid/acetonitrile).

Yield: 150 mg (98% purity, 52% of th.)

LC-MS (Method L1): R_(f)=1.38 min; MS (ESIpos): m/z=564 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (0.78), 0.008 (0.70),1.199 (4.33), 1.217 (9.13), 1.234 (4.62), 1.356 (0.52), 2.063 (0.43),2.073 (0.48), 2.084 (0.47), 2.099 (0.71), 2.107 (0.59), 2.114 (0.45),2.193 (0.49), 2.205 (0.59), 2.216 (0.59), 2.227 (0.52), 2.523 (0.52),3.049 (12.82), 4.052 (6.68), 4.134 (1.34), 4.152 (4.12), 4.170 (4.04),4.187 (1.27), 4.255 (1.01), 4.267 (1.21), 4.278 (1.65), 4.282 (1.70),4.293 (0.97), 5.257 (0.42), 5.271 (0.95), 5.291 (0.95), 5.305 (0.42),6.792 (1.74), 6.812 (1.94), 6.901 (0.87), 6.919 (1.84), 6.937 (1.07),7.154 (0.86), 7.157 (0.93), 7.175 (1.47), 7.193 (0.70), 7.196 (0.71),7.362 (1.56), 7.380 (1.46), 7.645 (16.00), 7.688 (1.26), 7.707 (1.75),7.728 (1.59), 7.840 (1.89), 7.842 (2.05), 7.857 (1.58), 7.860 (1.56),8.354 (1.72), 8.357 (1.80), 8.376 (1.63), 8.379 (1.60), 8.757 (6.02),9.197 (1.69), 9.217 (1.64).

N-{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}-N-methylglycine(Example 150)

EthylN-{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}-N-methylglycinate(from example 137) (35 mg, 62 μmol) was stirred in THF (0.3 ml), ethanol(0.3 ml) and 5 M aq. sodium hydroxide (50 μl, 250 μmol) for 1.5 h atambient temperature. The reaction mixture was acidified to pH 3 byaddition of 5 M formic acid and part of the solvents evaporated underreduced pressure. The formed precipitate was filtered off, washed withwater and dried in vacuo.

Yield: 27 mg (81% of th.)

LC-MS (Method L1): R_(f)=1.11 min; MS (ESIpos): m/z=536 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 2.132 (1.28), 2.205 (1.37),2.328 (0.59), 3.040 (16.00), 3.931 (0.61), 3.975 (4.59), 3.984 (4.71),4.281 (3.48), 5.309 (1.69), 5.326 (1.68), 6.779 (2.78), 6.799 (3.08),6.883 (1.42), 6.901 (2.80), 6.920 (1.72), 7.140 (1.56), 7.159 (2.50),7.175 (1.25), 7.348 (2.66), 7.365 (2.47), 7.643 (14.76), 7.660 (2.25),7.678 (2.82), 7.699 (1.88), 7.820 (3.02), 7.835 (2.42), 8.139 (1.05),8.304 (2.56), 8.326 (2.33), 8.755 (6.56).

8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(1H-1,2,3-triazol-1-yl)quinoline-3-carboxamide(Example 188)

and

8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(2H-1,2,3-triazol-2-yl)quinoline-3-carboxamide(Example 189)

A thick-walled microwave vessel was charged with4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4a) (145 mg, 0.3 mmol), 1,2,3-triazol (62 mg, 0.9 mmol), N-methylpyrrolidon (0.5 ml), triethylamine (84 μl, 0.6 mmol) and caesiumcarbonate (98 mg, 0.3 mmol). The vessel was capped and the mixtureheated under stirring at 100° C. for 2 h. 5 M formic acid (240 μl, 1.2mmol) and water (1.5 ml) were added and the precipitate filtered off anddiscarded. The filtrate was purified by prep. HPLC (C18, gradient: 0.1%aq. formic acid/acetonitrile).

Yield (example 188): 23 mg (15% of th.)

LC-MS (Method L1): R_(f)=1.18 min; MS (ESIneg): m/z=514 [M−H]⁻

¹H-NMR (400 MHz, DMSO-d6): δ [ppm]=9.23 (s, 1H), 9.12 (d, 1H), 8.65 (d,1H), 8.14 (d, 1H), 8.06 (dd, 1H), 7.80-7.88 (m, 1H), 7.68-7.76 (m, 3H),7.39-7.46 (m, 1H), 7.10-7.20 (m, 1H), 7.06 (d, 1H), 6.82-6.92 (m, 1H),6.76 (d, 1H), 4.98-5.09 (m, 1H), 4.18 (td, 1H), 4.00-4.12 (m, 1H), 2.02(br dd, 1H), 1.73-1.86 (m, 1H).

Yield (example 189): 73 mg (97% purity, 46% of th.)

LC-MS (Method L1): R_(f)=1.27 min; MS (ESIpos): m/z=516 [M+H]⁻

¹H-NMR (400 MHz, DMSO-d6): Shift [ppm]=9.12-9.22 (m, 2H), 8.35 (s, 2H),8.03 (dd, 1H), 7.87-7.96 (m, 1H), 7.78-7.87 (m, 1H), 7.66-7.76 (m, 2H),7.25 (d, 1H), 7.10-7.19 (m, 1H), 6.88-6.98 (m, 1H), 6.76 (d, 1H),4.98-5.14 (m, 1H), 4.07-4.29 (m, 2H), 2.02-2.14 (m, 1H), 1.94 (dtd, 1H).

tert-butyl1-{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}-L-prolinate (Example 243)

According to the procedure of example 137 the title compound wassynthesized from4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4a) (242 mg, 0.5 mmol) and tert-butyl L-prolinate (171 mg, 1.0mmol) by heating at 100° C. for 3 h.

Yield: 185 mg (60% of th.)

LC-MS (Method L1): R_(f)=1.39 min; MS (ESIpos): m/z=618 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 1.198 (16.00), 1.918 (0.63),1.932 (0.85), 1.945 (0.51), 4.260 (0.44), 6.788 (0.61), 6.808 (0.69),6.939 (0.64), 7.186 (0.52), 7.394 (0.55), 7.412 (0.51), 7.638 (5.73),7.655 (0.62), 7.676 (0.53), 7.815 (0.70), 7.832 (0.56), 8.315 (0.60),8.334 (0.55), 8.684 (2.06), 9.236 (0.58), 9.257 (0.57).

1-{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}-L-proline(Example 261)

A solution of hydrogen chloride in dioxan (1 ml, 4 M) was added to asolution of tert-butyl1-{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}-L-prolinate(from example 243) (155 mg, 0.25 mmol) in DICHLOROMETHANE (0.8 ml) andstirred overnight at ambient temperature. The volatiles were removedunder reduced pressure and the residue stirred with dichloromethane andwater. The separated water phase was extracted with dichloromethane, thecombined organic phases dried and evaporated. The residue was purifiedby prep. HPLC (C18, gradient: 0.1% aq. formic acid/acetonitrile).

Yield: 52 mg (37% of th.)

LC-MS (Method L1): R_(f)=0.91 min; MS (ESIpos): m/z=562 [M+H]⁺

¹H-NMR Peaklist (500 MHz, DMSO-d6) δ[ppm]: −0.007 (3.09), 0.006 (1.99),1.907 (2.42), 2.028 (0.58), 2.033 (0.60), 2.044 (0.71), 2.056 (0.83),2.166 (0.52), 2.175 (0.71), 2.185 (0.75), 2.193 (0.77), 2.204 (0.50),2.358 (0.89), 2.361 (1.22), 2.365 (0.93), 2.369 (0.58), 2.392 (0.70),2.407 (0.71), 2.514 (3.50), 2.518 (3.01), 2.522 (2.34), 2.631 (0.87),2.635 (1.14), 2.639 (0.81), 3.866 (0.46), 3.878 (1.06), 3.895 (0.91),4.183 (0.43), 4.188 (0.44), 4.205 (1.12), 4.224 (0.89), 4.229 (0.73),4.243 (0.75), 4.250 (1.08), 4.262 (0.91), 4.277 (0.46), 4.638 (0.83),4.649 (1.02), 4.654 (1.33), 4.665 (1.06), 5.254 (0.54), 5.264 (1.14),5.280 (1.10), 5.291 (0.50), 6.786 (2.22), 6.788 (2.18), 6.802 (2.42),6.804 (2.32), 6.919 (1.16), 6.921 (1.08), 6.933 (2.26), 6.935 (2.11),6.948 (1.31), 6.950 (1.18), 7.169 (1.12), 7.172 (1.16), 7.186 (1.76),7.200 (0.93), 7.203 (0.89), 7.388 (1.80), 7.403 (1.70), 7.629 (1.72),7.634 (4.02), 7.637 (8.89), 7.639 (16.00), 7.642 (4.87), 7.652 (2.18),7.654 (1.91), 7.669 (1.82), 7.806 (2.51), 7.809 (2.42), 7.821 (2.05),7.823 (1.86), 8.303 (1.86), 8.320 (1.72), 8.680 (8.25), 12.586 (0.91).

8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-[(2-hydroxyethyl)sulfanyl]quinoline-3-carboxamide(Example 264)

A thick-walled vessel was charged with4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4a) (121 mg, 250 μmol), DMSO (0.3 ml), 2-sulfanylethanol (39 mg,500 μmol) and triethylamine (87 μl, 630 μmol), capped and heated 2h at100° C. After cooling to ambient temperature 5 M formic acid (300 μl,1.5 mmol) was added, the mixture dissolved by adding acetonitrile andpurified by prep. HPLC (C18, gradient: 0.1% aq. formicacid/acetonitrile).

Yield: 95 mg (72% of th.)

LC-MS (Method L1): R_(f)=1.28 min; MS (ESIpos): m/z=525 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (2.66), 0.008 (2.57),2.119 (1.04), 2.128 (0.86), 2.366 (0.82), 2.710 (0.82), 3.060 (2.72),3.077 (6.64), 3.093 (3.50), 3.287 (2.70), 3.438 (1.04), 3.454 (2.48),3.468 (3.16), 3.481 (2.10), 3.497 (0.89), 4.254 (1.46), 4.263 (1.26),4.273 (2.24), 4.282 (2.43), 4.297 (1.35), 4.946 (2.06), 4.960 (4.56),4.974 (1.99), 5.291 (1.28), 5.310 (1.31), 6.781 (2.41), 6.784 (2.61),6.802 (2.74), 6.805 (2.88), 6.910 (1.33), 6.913 (1.46), 6.928 (2.63),6.932 (2.57), 6.947 (1.59), 6.950 (1.53), 7.151 (1.31), 7.156 (1.35),7.173 (2.21), 7.190 (1.24), 7.194 (1.13), 7.448 (2.17), 7.465 (2.06),7.627 (1.00), 7.632 (1.04), 7.658 (5.73), 7.662 (16.00), 7.666 (6.68),7.669 (3.41), 7.675 (1.22), 7.838 (1.93), 7.856 (2.97), 7.859 (2.35),7.877 (2.92), 7.929 (3.21), 7.932 (3.50), 7.946 (2.21), 7.950 (2.06),8.624 (2.97), 8.627 (2.97), 8.645 (2.70), 8.649 (2.50), 8.881 (10.45),9.155 (2.48), 9.175 (2.37).

8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-methoxyquinoline-3-carboxamide(Example 373)

Under argon atmosphere a solution of sodium methylate in methanol (140μl, 5.4 M, 780 μmol) was added dropwise to a solution of4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4a) (150 mg, 310 μmol) in N-methyl pyrrolidon (1 ml) and themixture stirred at ambient temperature for 40 min. Acetic acid (250 μl,5.0 M, 1.2 mmol) was added and the mixture purified by prep. HPLC (C18,gradient: 0.1% aq. formic acid/acetonitrile).

Yield: 94 mg (63% of th.)

LC-MS (Method L1): R_(f)=1.39 min; MS (ESIpos): m/z=479 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 4.172 (16.00), 4.245 (0.90),4.254 (1.07), 4.269 (1.49), 4.273 (1.51), 4.283 (0.86), 5.274 (0.83),5.293 (0.83), 5.754 (12.35), 6.793 (1.40), 6.796 (1.53), 6.814 (1.59),6.816 (1.66), 6.909 (0.74), 6.912 (0.74), 6.928 (1.55), 6.930 (1.54),6.946 (0.93), 6.949 (0.91), 7.159 (0.76), 7.163 (0.82), 7.180 (1.29),7.363 (1.33), 7.380 (1.25), 7.650 (0.88), 7.655 (2.07), 7.659 (2.33),7.670 (7.40), 7.675 (4.39), 7.702 (1.20), 7.720 (1.66), 7.723 (1.57),7.741 (1.47), 7.886 (1.69), 7.890 (1.80), 7.904 (1.44), 7.908 (1.42),8.296 (1.61), 8.299 (1.63), 8.317 (1.54), 8.320 (1.45), 8.811 (5.57),9.192 (1.36), 9.212 (1.34).

Synthesis of4-chloro-8-(3,5-dimethylphenyl)-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]quinoline-3-carboxamide(Example 1)

Step 1

ethyl-4-chloro-8-(3,5-dimethylphenyl)quinoline-3-carboxylate

Under argon atmosphere a flask was charged with ethyl8-bromo-4-chloroquinoline-3-carboxylate (330 mg, 1.05 mmol) (Zask, al.Bioorganic and Medicinal Chemistry Letters, 2003, 1487-1490; Laxmikant,al. US2013/210844), 3,5-dimethylbenzene boronic acid (189 mg, 1.26 mmol)and a degassed mixture of dioxan (6.6 ml) and water 1.3 ml). Thenpotassium carbonate (290 mg, 2.10 mmol) and1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (42.8 mg, 52.5 μmol) were added and the mixturestirred overnight at 50° C. The reaction mixture was filtered throughcelite and washed with ethyl acetate and water. The organic phase of thefiltrate was washed with water and brine, dried over sodium sulfate andevaporated under reduced pressure. The residue was purified by prep.HPLC (C18, gradient: 0.1% aq. formic acid/acetonitrile) and silica gelchromatography (cyclohexane/ethyl acetate—5:1).

Yield: 77.0 mg (21% of th.)

LC-MS (Method L1): R_(f)=1.43 min; MS (ESIpos): m/z=340 [M+H]⁺

NMR: ¹H-NMR (400 MHz, DMSO-d₆): δ [ppm]=9.13 (s, 1H), 8.42 (dd, 1H),7.87-7.96 (m, 2H), 7.20 (s, 2H), 7.07 (s, 1H), 4.44 (q, 2H), 2.35 (s,6H), 1.38 (t, 3H).

Step 2

4-chloro-8-(3,5-dimethylphenyl)quinoline-3-carboxylic acid

To ethyl-4-chloro-8-(3,5-dimethylphenyl)quinoline-3-carboxylate (step 1)(84.0 mg, 247 μmol) in 0.5 ml ethanol and 0.5 ml THF was added anaqueous solution of sodium hydroxide (5 M, 150 μl, 740 μmol) and themixture stirred overnight at ambient temperature. The solvents wereremoved under reduced pressure, the residue was dissolved in DMSO and 5M formic acid and purified via prep. HPLC (C18, gradient: 0.1% aq.formic acid/acetonitrile) yielding an off-white solid.

Yield: 75.0 mg (97% of th).

LC-MS (Method L1): R_(f)=1.15 min; MS (ESIpos): m/z=312 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 2.346 (16.00), 7.062 (1.52),7.189 (3.52), 7.884 (1.52), 7.895 (1.68), 7.902 (3.49), 8.396 (0.99),8.403 (0.92), 8.414 (0.88), 8.421 (0.87), 9.116 (2.83).

Step 3

4-chloro-8-(3,5-dimethylphenyl)-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]quinoline-3-carboxamide(Example 1)

4-Chloro-8-(3,5-dimethylphenyl)quinoline-3-carboxylic acid (step 2)(71.0 mg, 228 μmol) in 1.2 ml THF was treated with(1S)-1,2,3,4-tetrahydronaphthalen-1-amine (36.9 mg, 251 μmol) andtriethylamine (190 μl, 1.4 mmol) and stirred at 60° C. for 10 min. Thena solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane2,4,6-trioxide in ethylacetate (200 μl, 50% content, 340 μmol) wasadded, the heating removed and the mixture stirred overnight at ambienttemperature. Water and 5 M formic acid (0.6 ml) were added and thesolvents removed under reduced pressure. The residue was purified byprep. HPLC (C18, gradient: 0.1% aq. formic acid/acetonitrile).

Yield: 20.0 mg (20% of th)

LC-MS (Method L1): R_(f)=1.42 min; MS (ESIpos): m/z=441 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (4.41), 0.008 (4.06),2.342 (16.00), 2.759 (1.07), 7.059 (1.60), 7.111 (0.66), 7.128 (1.05),7.183 (4.61), 7.195 (1.69), 7.202 (0.82), 7.207 (0.96), 7.422 (0.89),7.438 (0.75), 7.855 (4.02), 7.865 (2.24), 7.869 (2.26), 8.303 (1.26),8.314 (1.10), 8.317 (1.07), 8.328 (1.10), 8.874 (5.11), 9.102 (0.96),9.123 (0.96).

Synthesis of8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)quinoline-3-carboxamide(Example 52)

Step 1

8-bromo-4-chloroquinoline-3-carboxylic acid

To a suspension of ethyl-8-bromo-4-chlorquinoline-3-carboxylate (9.44 g,30.0 mmol) in THF (65 ml) was added an aqueous sodiumhydroxid solution(12 ml, 10 M, 120 mmol) and the mixture stirred vigorously at ambienttemperature. After 5 hours, water (12 ml) was added and the mixturestirred overnight at ambient temperature. The supernatant was decantedfrom the amorphous precipitate which had formed on the wall of the flaskand discarded. The precipitate was dried in vacuo, yielding the sodiumsalt of the title compound.

LC-MS (Method L1): R_(f)=0.70 min; MS (ESIpos): m/z=285 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d₆): δ [ppm]=8.98 (s, 1H), 8.29 (dd, 1H),8.16-8.23 (m, 1H), 7.64 (t, 1H).

The remaining wet solid was dissolved in water (250 ml) at 60° C. andformic acid (57 ml, 5.0 M, 280 mmol) was added under vigorous stirringresulting in a pH value of 3 and formation of a precipitate. The mixturewas cooled to ambient temperature, the precipitate filtered off, washedwith water and dried in vacuo at 40° C.

Yield: 7.0 g (98% purity, 80% of th.)

LC-MS (Method L1): R_(f)=0.70 min; MS (ESIpos): m/z=285 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d₆): δ [ppm]=14.12 (br s, 1H), 9.25 (s, 1H), 8.42(d, 1H), 8.36 (d, 1H), 7.75 (t, 1H).

Step 2

8-bromo-4-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide

8-Bromo-4-chloroquinoline-3-carboxylic acid (step 1) (7.00 g, 24.4 mmol)was dissolved in THF by stirring in an oilbath of 50° C. for 10 min. Theheating was removed, (4S)-chroman-4-amine hydrochloride (5.44 g, 29.3mmol), N,N-diisopropyl-ethyl-amine (17 ml, 98 mmol) and a solution of2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide in ethylacetate (23 ml, 50 content, 39 mmol) were added, which caused anincrease in temperature to 45° C. Stirring was continued for 30 min andwater (300 ml) was added under continuous stirring to supportprecipitation of a solid. The precipitate was collected, washed withwater and dried in vacuo.

Yield: 9.50 g (93% of th.)

LC-MS (Method L1): R_(f)=1.01 min; MS (ESIneg): m/z=417 [M+H]⁻

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 2.047 (0.74), 2.054 (0.99),2.063 (1.54), 2.070 (1.66), 2.081 (1.85), 2.088 (1.86), 2.097 (2.49),2.104 (2.18), 2.113 (1.49), 2.120 (1.08), 2.197 (1.06), 2.206 (1.61),2.218 (2.41), 2.231 (2.17), 2.239 (2.10), 2.252 (1.56), 2.264 (1.01),2.273 (0.71), 2.328 (0.42), 2.670 (0.47), 4.205 (1.18), 4.212 (1.43),4.233 (3.76), 4.240 (2.80), 4.253 (3.08), 4.261 (2.42), 4.277 (2.42),4.285 (3.12), 4.293 (2.75), 4.302 (3.10), 4.313 (1.33), 4.321 (1.40),4.329 (1.04), 5.266 (1.51), 5.281 (3.35), 5.300 (3.35), 5.315 (1.47),6.793 (5.60), 6.814 (6.35), 6.922 (2.99), 6.940 (6.44), 6.959 (3.78),7.162 (3.04), 7.165 (3.11), 7.183 (5.15), 7.201 (2.48), 7.382 (5.42),7.401 (5.04), 7.713 (4.62), 7.733 (8.03), 7.754 (5.29), 8.312 (6.79),8.324 (8.26), 8.327 (8.69), 8.345 (6.64), 9.042 (16.00), 9.264 (4.77),9.285 (4.67).

Step 3

8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)quinoline-3-carboxamide

To a suspension of8-bromo-4-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 2) (9.50 g, 22.7 mmol) in THF (70 ml), morpholine (6.0 ml, 68mmol) and 1,4-diazabicyclo[2.2.2]octane (2.55 g, 22.7 mmol) were addedand stirred for 1.5 h at 80° C. bath temperature. Water was added (30ml) and the THF evaporated under reduced pressure. More water was addedand the suspension stirred first at 50° C. then at ambient temperature.The precipitate was filtered off, washed with water and dried in vacuo.

Yield: 10.5 g (98% of th.)

LC-MS (Method L1): R_(f)=0.92 min; MS (ESIneg): m/z=466 [M−H]⁻

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.149 (0.41), −0.008 (4.42),0.008 (3.18), 2.041 (0.54), 2.048 (0.76), 2.056 (1.13), 2.063 (1.19),2.076 (1.30), 2.091 (1.80), 2.098 (1.57), 2.106 (1.11), 2.197 (0.74),2.206 (1.17), 2.218 (1.70), 2.231 (1.59), 2.240 (1.58), 2.253 (1.13),2.262 (0.74), 2.274 (0.52), 2.327 (0.60), 2.366 (0.49), 2.523 (2.30),2.669 (0.66), 2.710 (0.48), 3.217 (0.69), 3.228 (1.18), 3.248 (4.71),3.258 (11.00), 3.269 (11.28), 3.279 (5.00), 3.842 (8.92), 3.853 (14.13),3.864 (8.07), 4.214 (0.80), 4.221 (1.01), 4.242 (2.68), 4.249 (2.03),4.263 (2.41), 4.271 (2.08), 4.276 (2.00), 4.286 (2.44), 4.293 (2.07),4.302 (2.18), 4.314 (0.86), 4.321 (0.96), 4.329 (0.65), 5.245 (1.10),5.259 (2.45), 5.279 (2.44), 5.292 (1.06), 6.797 (4.29), 6.815 (4.84),6.927 (2.26), 6.929 (2.16), 6.946 (4.75), 6.964 (2.87), 7.164 (2.33),7.167 (2.40), 7.185 (3.85), 7.202 (1.91), 7.206 (1.79), 7.385 (4.05),7.403 (3.77), 7.499 (3.74), 7.518 (5.40), 7.538 (4.06), 8.123 (4.80),8.125 (5.04), 8.142 (4.71), 8.144 (4.51), 8.197 (4.92), 8.199 (4.64),8.218 (4.71), 8.753 (16.00), 9.177 (3.99), 9.197 (3.89).

Step 4

8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)quinoline-3-carboxamide(Example 52)

Under argon atmosphere potassium carbonate (1.29 g, 9.31 mmol) wasdissolved in a degassed 5:1 mixture of dioxan and water (21 ml) bysonification.1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (190 mg, 0.23 mmol) and8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)quinoline-3-carboxamide(step 3) (2.18 g, 4.65 mmol) were added, followed by 2,3-dichlorobenzeneboronic acid (977 mg, 5.12 mmol). The vessel was closed and stirred at80° C. bath temperature for 2.5 h. Water was added and the mixtureextracted with ethyl acetate. The organic phases were dried andevaporated under reduced pressure. The residue was purified bycolumn-chromatography on silica (10 g), eluent: cyclohexane/ethylacetate (15-35%). The obtained solid was stirred in a mixture of MTBE(30 ml) and methanol (1.5 ml), filtered off an dried in vacuo.

Yield: 2.03 g (82% of th.)

LC-MS (Method L1): R_(f)=1.13 min; MS (ESIpos): m/z=534 [M+H]⁺

¹H-NMR Peaklist (600 MHz, DMSO-d6) δ[ppm]: 2.056 (0.40), 2.199 (0.43),2.208 (0.44), 2.214 (0.44), 3.269 (0.65), 3.280 (1.04), 3.289 (1.15),3.300 (1.36), 3.307 (1.17), 3.321 (0.61), 3.335 (16.00), 4.233 (0.78),4.237 (0.53), 4.247 (0.59), 4.251 (0.49), 4.261 (0.49), 4.267 (0.62),4.272 (0.54), 4.278 (0.63), 5.239 (0.42), 5.246 (0.54), 5.260 (0.42),6.781 (1.24), 6.794 (1.32), 6.911 (0.70), 6.915 (0.74), 6.928 (0.40),7.150 (0.59), 7.162 (0.96), 7.175 (0.49), 7.310 (0.47), 7.312 (0.47),7.323 (0.59), 7.324 (0.57), 7.336 (0.53), 7.338 (0.53), 7.348 (0.71),7.350 (0.72), 7.357 (1.04), 7.370 (0.95), 7.420 (0.46), 7.432 (1.04),7.445 (1.07), 7.457 (0.42), 7.664 (0.76), 7.676 (1.51), 7.690 (2.57),7.693 (1.60), 7.704 (2.49), 7.716 (0.68), 8.281 (1.15), 8.283 (1.14),8.295 (1.07), 8.297 (1.02), 8.588 (1.70), 8.595 (1.82), 9.166 (0.54),9.180 (1.03), 9.195 (0.56).

Synthesis of8-(3-chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethyl-amino)-7-fluoroquinoline-3-carboxamide(Example 141)

Step 1

ethyl 8-bromo-7-fluoro-4-hydroxyquinoline-3-carboxylate

A mixture of 2-bromo-3-fluoroaniline (24.89 g, 131 mmol) and diethylethoxymethylenemalonate (28.33 g, 131 mmol, 26 mL) was stirred at roomtemperature for 16 h. Stirring was continued at 250° C. under vacuo (60mbar) for 6 h. The reaction mixture was allowed to cool to roomtemperature. The solid residue was stirred in refluxing ethyl acetate(400 mL). The precipitate was filtered off and washed with ethylacetate. The solid was stirred in a refluxing mixture of ethanol (400mL) and methanol (40 mL). The hot suspension was filtered off. The solidwas washed with ethanol and dried on air.

Yield: 28.60 g (83 mmol, 63% of th.)

LC-MS (Method L2): R_(f)=1.73 min, m/z=314/316 (M+H)⁺

¹H-NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.45 (s, 1H), 8.22 (m, 1H),7.50-7.39 (m, 1H), 4.23 (d, J=7.1 Hz, 2H), 1.28 (t, J=7.1 Hz, 3H).

Step 2

ethyl 8-bromo-4-chloro-7-fluoroquinoline-3-carboxylate

To stirring phosphorus oxychloride (38.4 g, 250 mmol, 23 mL) was addedethyl 8-bromo-7-fluoro-4-hydroxyquinoline-3-carboxylate (step 1) (23.6g, 75 mmol). The resulting suspension was stirred at 80° C. for 1 h. Themixture was allowed to cool to room temperature and was poured out intovigorously stirred ice-water (100 mL). The resulting mixture was leftstanding for two days at room temperature. The precipitate was collectedby filtration and was washed with water until the filtrate was neutral.Solids were triturated in a mixture of diethyl ether and diisopropylether (1:1; 1 L). Solids were filtered off. The filtrate wasconcentrated in vacuo at 25° C. After co-evaporation of the residue withtoluene 21.3 g (64 mmol, 85% of theory) of the title compound wereobtained.

Yield: 21.3 g (64 mmol, 85% of th.)

LC-MS (Method L2): R_(f)=2.18 min, m/z=332/334 (M+H)⁺

Step 3

ethyl 8-bromo-4-(dimethylamino)-7-fluoroquinoline-3-carboxylate

To a solution of ethyl 8-bromo-4-chloro-7-fluoroquinoline-3-carboxylate(step 2) (14.31 g, 43 mmol) in dry tetrahydrofuran (150 mL) were addedtriethyl amine (8.71 g, 86 mmol, 12 mL) and dimethylamine (2 M intetrahydrofuran; 48 mmol, 24 mL). The reaction mixture was stirred for16 h at room temperature. Solids were filtered off and washed withtetrahydrofuran. The filtrate was concentrated in vacuo to afford thetitle compound.

Yield: 12.66 g (37 mmol, 86% of th.)

LC-MS (Method L2): R_(f)=1.75 min, m/z=341/343 (M+H)⁺

¹H-NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.28 (dd, J=9.4, 6.1 Hz, 1H),7.63 (dd, J=9.4, 8.2 Hz, 1H), 4.39 (q, J=7.1 Hz, 2H), 3.07 (s, 6H), 1.36(t, J=7.1 Hz, 3H).

Step 4

ethyl 8-bromo-4-(dimethylamino)-7-fluoroquinoline-3-carboxylatehydrochloride

To a solution of ethyl8-bromo-4-(dimethylamino)-7-fluoroquinoline-3-carboxylate (step 3) (14.0g, 41 mmol) in tetrahydrofuran (100 mL) was added a solution oflithiumhydroxide monohydrate (11.5 g, 274 mmol) in water (100 mL). Themixture was stirred for 16 h at 75° C. and was allowed to cool to roomtemperature. Layers were separated and the aqueous layer was extractedwith tetrahydrofuran (2×150 mL). Combined organic layers wereconcentrated in vacuo and hydrochloric acid (4 M; 100 mL) was added. Thesolid was filtered off, washed with water and diethyl ether and wasdried on air to afford the title compound.

Yield: 10.6 g (30 mmol, 74% of th.)

LC-MS (Method L2): R_(f)=1.21 min, m/z=313/315 (M+H)+

¹H-NMR (400 MHz, DMSO-d6) δ 8.73 (s, 1H), 8.41 (dd, J=9.4, 5.7 Hz, 1H),7.66 (dd, J=9.4, 8.1 Hz, 1H), 3.35 (s, 6H) [acidic protons were notdetected].

Step 5

8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-7-fluoroquinoline-3-carboxamide

To a solution of8-bromo-4-(dimethylamino)-7-fluoroquinoline-3-carboxylic acidhydrochloride (step 4) (2.00 g, 5.7 mmol) in N,N-dimethylformamide (50mL) were added1-[bis(dimethylamino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (2.18 g, 5.7 mmol) andN,N-diisopropylethylamine (4.21 g, 32.6 mmol, 5.7 mL). The mixture wasstirred at room temperature for 1 h. (4S)-Chroman-4-amine hydrochloride(1.06 g, 5.7 mmol) was added. The reaction mixture was stirred for 16 hat room temperature. The mixture was poured out into water (200 mL).Solids were filtered off, washed with water and were dried in vacuo.After co-evaporation with toluene and ethyl acetate the title compoundwas obtained.

Yield: 1.90 g (4.3 mmol, 75% of th.)

LC-MS (Method L2): R_(f)=1.78 min, m/z=444/446 (M+H)⁺

¹H-NMR (400 MHz, DMSO-d6) δ 9.12 (d, J=8.1 Hz, 1H), 8.70 (s, 1H), 8.23(dd, J=9.4, 6.1 Hz, 1H), 7.59 (dd, J=9.3, 8.3 Hz, 1H), 7.37 (d, J=6.8Hz, 1H), 7.22-7.14 (m, 1H), 6.98-6.90 (m, 1H), 6.81 (dd, J=8.2, 1.0 Hz,1H), 5.29-5.20 (m, 1H), 4.34-4.19 (m, 2H), 3.06 (s, 6H), 2.27-2.15 (m,1H), 2.11-2.00 (m, 1H).

Step 6

8-(3-chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethyl-amino)-7-fluoroquinoline-3-carboxamide(Example 141)

In an 8 mL screw capped vial, to a degassed (1 min, nitrogen) mixture of8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-7-fluoroquinoline-3-carboxamide(100 mg, 0.225 mmol), (3-chlorophenyl)boronic acid (42 mg, 0.270 mmol)and sodium carbonate (72 mg, 0.675 mmol) in a mixture of tetrahydrofuran(1.30 mL) and water (0.25 mL) was added1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (3 mg,0.005 mmol). The reaction mixture was stirred for 16 h at 60° C. and wascooled to room temperature. Water (5 mL) was added and the aqueous layerwas extracted with dichloromethane (3×3 mL) by phase separator. Solventswere removed in vacuo. Purification by flash column chromatography(heptane, 5%-35% ethyl acetate) afforded the title compound.

Yield: 56 mg (0.118 mmol, 52% of th.)

LC-MS (Method L2): R_(f)=3.03 min, m/z=476 (M+H)⁺

¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J=8.2 Hz, 1H), 8.58 (s, 1H), 8.27(dd, J=9.4, 6.2 Hz, 1H), 7.60 (t, J=9.3 Hz, 1H), 7.55-7.45 (m, 3H),7.43-7.31 (m, 2H), 7.20-7.12 (m, 1H), 6.95-6.88 (m, 1H), 6.83-6.76 (m,1H), 5.28-5.19 (m, 1H), 4.32-4.19 (m, 2H), 3.07 (s, 6H), 2.25-2.14 (m,1H), 2.09-1.98 (m, 1H).

Synthesis of8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxamide (Example 331)

Step 1

ethyl 8-bromo-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxylate

A flask was charged with ethyl 8-bromo-4-chloroquinoline-3-carboxylate(1.26 g, 4 mmol) (Zask, al. Bioorganic and Medicinal Chemistry Letters,2003, 1487-1490; Laxmikant, al. US2013/210844), 1-methyl-3-oxetanamine(0.42 g, 4 mmol), N,N-diisopropyl-ethylamin (0.62 g, 4.8 mmol) in 40 mLAcetonitril. The reaction mixture was refluxed for 24 hours. Then thesolvent was removed under reduced pressure and the remaining materialwas dissolved in ethyl acetate and washed twice with water. The organicphase was separated, dried over calcium sulfate, filtered and thefiltrate was removed under reduced pressure. The resulting residue waspurified by reverse phase column chromatography (eluentwater/acetonitrile gradient).

Yield: 1.2 g (3.2 mmol, 82% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.20 (d, 1H), 8.14 (d, 1H),7.55 (dd, 1H), 4.72-4.62 (m, 5H, oxetanyl), 4.43-4.38 (q, 2H), 3.10 (s,3H), 1.37 (t, 3H).

Step 2

ethyl8-(2,3-dichlorophenyl)-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxylate

In an microwave vial, to a degassed (1 min, argon) mixture of ethyl8-bromo-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxylate (step 1)(500 mg, 1.37 mmol), (2,3-dichlorophenyl)boronic acid (261 mg, 1.37mmol), an aqueous solution of cesium carbonate (2M, 1.37 mL, 2.74 mmol)and dioxane (12.5 mL) was added1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (111 mg,0.14 mmol). The reaction mixture was treated in a Biotage microwave ovenfor 25 minutes at 100° C. The reaction mixture was filtered via a sodiumsulfate/silica gel cartridge and purified by reverse phase columnchromatography (eluent water/acetonitrile gradient).

Yield: 600 mg (98% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.21 (t, 1H), 7.74 (d, 2H),7.71 (d, 1H), 7.45 (t, 1H), 7.36 (d, 1H), 4.76-4.65 (m, 5H, oxetanyl),4.40-4.34 (q, 2H), 3.14 (s, 3H), 1.34 (t, 3H).

Step 3

8-(2,3-dichlorophenyl)-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxylicacid

Ethyl8-(2,3-dichlorophenyl)-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxylate(step 2) (580 mg, 1.34 mmol) was dissolved in 20 mL dioxane and mixedwith LiOH (35.4 mg, 1.48 mmol) in 5 mL water. The reaction mixture washeated for 16 hours at 60° C. The dioxane was removed under reducedpressure, the remaining solution was taken into a mixture of ethylacetate and water. The aqueous phase was separated and treated with 1NHCl until pH 5. This acidified solution was extracted twice with ethylacetate, the combined extracts were dried, filtered and the solvent wasremoved under reduced pressure. The obtained compound was used in thenext step without further purification.

Yield: 570 mg (99% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H, COOH), 8.73 (s, 1H),8.24-8.22 (dd, 1H), 7.23-7.68 (m, 3H), 7.44 (t, 1H), 7.37-7.35 (dd, 1H),4.76-4.65 (m, 5H, oxetanyl), 3.13 (s, 3H).

Step 4

8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-[methyl(oxetan-3-yl)amino]-quinoline-3-carboxamide(Example 331)

A flask was charged with8-(2,3-dichlorophenyl)-4-[methyl(oxetan-3-yl)amino]quinoline-3-carboxylicacid (step 3) (260 mg, 0.645 mmol), (4S)-chroman-4-amine hydrochloride(131.7 mg, 0.71 mmol), N,N-diisopropyl ethylamine (250 mg, 1.93 mmol),4-(N,N-dimethylamino) pyridine (39.4 mg, 0.32 mmol),1-hydroxy-1H-benzotriazole (43.5 mg, 0.32 mmol) and1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (123.6 mg,0.645 mmol) in 10 mL dichloromethane. The reaction mixture was stirredat ambient temperature overnight, then mixed with water, thedichloromethane phase was separated, dried via a sodium sulfate/silicagel cartridge and the solvent was removed under reduced pressure. Theresidue was purified by reverse phase column chromatography (eluentwater/acetonitrile gradient) to obtain the title compound.

Yield: 130 mg (0.24 mmol, 37% of th.)

¹H-NMR Peaklist (399,9532 MHz, DMSO): δ=9.1403 (1.94); 9.1288 (2);9.1208 (2.32); 9.1103 (1.85); 8.6012 (10.54); 8.4715 (0.58); 8.3155(1.57); 8.2143 (2.25); 8.1975 (2.56); 8.1729 (1.06); 7.7323 (2.07);7.7127 (5.31); 7.6894 (10.46); 7.6737 (1.95); 7.4635 (1.67); 7.4521(1.74); 7.4433 (2.94); 7.4332 (2.77); 7.4235 (2.08); 7.4143 (1.65);7.3824 (1.86); 7.3618 (4.63); 7.3428 (4.44); 7.3225 (1.63); 7.1895(1.81); 7.171 (3.64); 7.1535 (2.27); 6.9433 (2.6); 6.9255 (4.32); 6.9084(2.02); 6.8059 (4.77); 6.7848 (4.45); 6.5782 (0.9); 5.2488 (1.97); 5.237(2); 4.725 (1.91); 4.697 (7.04); 4.6722 (5.48); 4.6575 (5.6); 4.5955(1.22); 4.5844 (1.61); 4.2921 (2.17); 4.2752 (3.94); 4.2675 (3.64);4.2552 (2.23); 4.2471 (2.41); 4.2281 (0.89); 3.3183 (319.34); 3.2701(0.87); 3.2496 (0.61); 3.1747 (0.71); 3.081 (16); 3.0759 (15.54); 2.9497(1.08); 2.6703 (8.96); 2.5893 (0.63); 2.5051 (1239.6); 2.5012 (1583.24);2.4971 (1204.24); 2.3276 (9.3); 2.2832 (0.88); 2.2475 (1.34); 2.2286(1.72); 2.2205 (1.78); 2.1313 (0.96); 2.074 (5.92); 2.0168 (0.96);1.2694 (0.87); 1.169 (4.47); 1.0034 (0.71); 0.9887 (0.75); 0.1463(2.93); −0.0001 (642.47); −0.0792 (0.67); −0.1497 (3.13); −3.3083(0.55).

Synthesis of8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-ethoxyquinoline-3-carboxamide(Example 134)

Step 1

8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-hydroxyquinoline-3-carboxamide

A solution of 8-(3,5-dichlorophenyl)-4-hydroxyquinoline-3-carboxylicacid (5.50 g, 16.5 mmol) in THF was treated stirred with(1S)-indan-1-amine (2.5 ml, 20 mmol) and trimethylamine (9.2 ml, 66mmol) for 10 min at ambient temperature. Then a solution of2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide inethylacetate (19.6 ml, 50% content, 33 mmol) was added an stirredovernight at ambient temperature. Water (100 ml) was added and the THFevaporated under reduced pressure. More water and ethyl acetate wereadded and the mixture cleared by filtration. The aqueous phase wasextracted with ethyl acetate and the combined organic phases dried andevaporated under reduced pressure. The residue was purified by columnchromatography on silica (340 g) with cyclohexane/ethyl acetate(15-40%). Two fractions were isolated:

Yield: 3.0 g (98% purity, 40% of th.) and 0.69 g (94% purity, 9% of th.)

LC-MS (Method L1): R_(f)=1.27 min; MS (ESIneg): m/z=447 [M+H]⁻

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 1.849 (1.87), 1.868 (2.39),1.880 (2.59), 1.900 (2.50), 1.921 (1.16), 2.578 (3.74), 2.588 (3.08),2.841 (1.03), 2.862 (1.82), 2.882 (2.65), 2.902 (3.54), 2.922 (2.00),2.977 (2.56), 2.990 (2.71), 2.999 (2.71), 3.029 (1.74), 5.474 (1.16),5.493 (3.52), 5.512 (3.77), 5.531 (1.67), 7.197 (1.27), 7.214 (3.91),7.233 (6.17), 7.256 (5.56), 7.280 (7.00), 7.298 (9.89), 7.316 (4.52),7.521 (2.83), 7.540 (5.61), 7.560 (4.06), 7.626 (14.53), 7.631 (16.00),7.695 (5.87), 7.713 (5.06), 7.804 (5.42), 8.297 (4.58), 8.318 (4.68),8.611 (4.35), 8.624 (4.69), 10.285 (4.44), 10.304 (4.72), 11.637 (3.53).

Step 2

8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-ethoxyquinoline-3-carboxamide(Example 134)

8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-hydroxyquinoline-3-carboxamide(step 1) (70.0 mg, 156 μmol), ethanol (27 μl, 470 μmol),triphenylphosphine (61.3 mg, 234 μmol) anddiisopropyl-(E)-diazene-1,2-dicarboxylate (46 μl, 230 μmol) were stirredin THF (1 ml) at ambient temperature for 6 h. 5 M formic acid (93 μl,470 μmol) was added, the solvent evaporated and the residue purified byprep. HPLC (C18, gradient: 0.1% aq. formic acid/acetonitrile).

Yield: 40 mg (92% purity, 49% of th.)

LC-MS (Method L7): R_(f)=2.60 min; MS (ESIpos): m/z=477 [M+H]⁺

¹H-NMR (Peaklist) (500 MHz, DMSO-d6) δ[ppm]: −0.007 (4.15), 0.007(3.67), 1.235 (1.26), 1.395 (7.56), 1.409 (16.00), 1.423 (7.72), 1.950(1.18), 1.966 (1.28), 1.975 (1.34), 1.991 (1.30), 2.522 (1.98), 2.853(1.24), 2.869 (1.51), 2.885 (1.92), 2.901 (0.85), 2.981 (1.03), 2.989(1.09), 2.999 (1.11), 3.006 (1.07), 3.013 (0.81), 3.286 (5.84), 4.352(1.51), 4.354 (1.53), 4.366 (4.56), 4.368 (4.83), 4.380 (4.46), 4.383(4.79), 4.394 (1.38), 4.396 (1.51), 5.533 (0.78), 5.549 (2.29), 5.564(2.27), 5.580 (0.78), 5.754 (0.91), 7.227 (2.02), 7.231 (3.49), 7.238(4.46), 7.245 (4.52), 7.249 (3.34), 7.260 (1.11), 7.278 (2.99), 7.290(1.65), 7.294 (1.20), 7.400 (2.19), 7.406 (2.33), 7.417 (2.00), 7.654(2.35), 7.658 (5.35), 7.661 (4.98), 7.674 (15.77), 7.678 (10.55), 7.714(2.52), 7.729 (3.39), 7.731 (3.32), 7.745 (2.97), 7.889 (3.47), 7.891(3.80), 7.903 (3.01), 7.906 (3.03), 8.304 (3.32), 8.307 (3.57), 8.321(3.16), 8.324 (3.16), 8.842 (11.93), 8.998 (2.83), 9.015 (2.77).

Synthesis of8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-ethylquino-line-3-carboxamide (Example 350)

A solution of diethylzinc in heptane (400 μl, 1.0 M, 400 μmol) was addeddropwise to a mixture of4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4, example 4) (97 mg, 200 μmol) and1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (32.7 mg, 40.0 μmol) in dioxan (2 ml) andstirred at 90° C. overnight under an argon atmosphere. 5 M formic acid(160 μl, 5.0 M, 800 μmol) and DMSO (1 ml) were added and the filteredmixture was purified twice by preparative HPLC (C18, gradient: 0.1% aq.formic acid/acetonitrile).

Yield: 52 mg (98% purity, 53% of th.)

LC-MS (Method L1): R_(f)=1.35 min; MS (ESIpos): m/z=477 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 1.303 (2.43), 1.322 (5.61),1.341 (2.50), 3.252 (2.09), 3.271 (2.06), 4.250 (1.06), 4.259 (1.62),4.268 (1.95), 4.275 (1.54), 4.284 (1.06), 5.305 (0.92), 5.325 (0.92),6.783 (1.53), 6.785 (1.66), 6.803 (1.75), 6.806 (1.83), 6.911 (0.78),6.914 (0.83), 6.930 (1.72), 6.932 (1.71), 6.948 (1.03), 6.951 (1.00),7.149 (0.86), 7.153 (0.89), 7.170 (1.43), 7.350 (1.48), 7.370 (1.41),7.652 (16.00), 7.752 (1.09), 7.770 (1.68), 7.791 (1.47), 7.871 (1.93),7.874 (2.04), 7.889 (1.44), 7.892 (1.42), 8.319 (1.50), 8.322 (1.58),8.340 (1.43), 8.343 (1.39), 8.839 (5.77), 9.102 (1.60), 9.123 (1.55).

Isolation of8-(3-chloro-5-ethylphenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-ethylquinoline-3-carboxamide(Example 351)

The preparative HPLC separation described in example 350 yielded thetitle compound as a by-product.

Yield: 12 mg (100% purity, 13% of th.)

LC-MS (Method L1): R_(f)=1.36 min; MS (ESIpos): m/z=471 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d₆): δ [ppm]=9.10 (d, 1H), 8.81 (s, 1H), 8.29 (dd,1H), 7.72-7.83 (m, 2H), 7.46 (t, 1H), 7.31-7.40 (m, 3H), 7.17 (t, 1H),6.93 (td, 1H), 6.79 (dd, 1H), 5.27-5.35 (m, 1H), 4.22-4.31 (m, 2H),3.21-3.29 (m, 2H) superimpose by water signal, 2.64-2.73 (m, 2H),2.16-2.26 (m, 1H), 2.01-2.11 (m, 1H), 1.32 (t, 3H), 1.23 (t, 3H).

Synthesis of8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(prop-1-en-2-yl)quinoline-3-carboxamide(Example 317)

Under argon atmosphere and continuous sonication potassium carbonate(571 mg, 4.13 mmol) was dissolved in a thick-walled vessel in a 5:1degassed mixture of dioxan and water (7.0 ml).1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (84.4 mg, 103 μmol) and4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(step 4, example 4) (1.00 g, 2.07 mmol) were added, followed by4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (0.49 ml, 4.1mmol). The vessel was capped and stirred at 80° C. for 4 h. 5 M formicacid (1.3 ml) and water were added and the mixture extracted with ethylacetate. The organic phases were dried and evaporated under reducedpressure. The residue was purified by column chromatography on silica(50 g), eluent: cyclohexane/ethyl acetate (7-16%).

Yield: 885 mg (87% of th.)

LC-MS (Method L1): R_(f)=1.39 min; MS (ESIpos): m/z=489 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d6): Shift [ppm]=8.88-9.00 (m, 2H), 8.04 (dd, 1H),7.90 (dd, 1H), 7.76 (dd, 1H), 7.67 (s, 3H), 7.32 (br d, 1H), 7.11-7.22(m, 1H), 6.92 (t, 1H), 6.78 (dd, 1H), 5.54 (s, 1H), 5.18-5.30 (m, 1H),5.03 (br s, 1H), 4.16-4.33 (m, 2H), 2.12-2.26 (m, 4H), 1.95-2.06 (m,1H).

Synthesis of8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-isopropyl-quinoline-3-carboxamide(Example 359)

Under argon atmosphere8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(prop-1-en-2-yl)quinoline-3-carboxamide(from example 317) (150 mg, 306 μmol) was dissolved in ethyl acetate (7ml) and ethanol (3.5 ml). Pd on charcoal (44 mg, 10%) was added and themixture hydrogenated under normal pressure at ambient temperature for1.5 h. The catalyst was filtered off through Celite, washed with anethyl acetate/ethanol mixture (2:1) and the filtrate evaporated underreduced pressure. The residue was purified two times by prep. HPLC (C18,gradient: 0.1% aq. formic acid/acetonitrile).

Yield: 64 mg (42% of th.)

LC-MS (Method L1): R_(f)=1.41 min; MS (ESIpos): m/z=491 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d6): Shift [ppm]=9.12 (d, 1H), 8.76 (s, 1H), 8.45(d, 1H), 7.85 (d, 1H), 7.74 (t, 1H), 7.61-7.66 (m, 3H), 7.36 (d, 1H),7.17 (t, 1H), 6.93 (t, 1H), 6.79 (d, 1H), 5.25-5.31 (m, 1H), 4.21-4.31(m, 2H), 3.82-3.92 (m, 1H), 2.21 (td, 1H), 2.06 (ddd, 1H), 1.56 (br d,3H), 1.53 (br d, 3H).

Synthesis of ethylcyano{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}acetate(Example 354)

Under argon atmosphere sodium hydride (165 mg, 60% content, 4.13 mmol)was added at 0° C. to a solution of ethyl-cyanoacetate (0.44 ml, 4.1mmol) in dry N-methyl pyrrolidon, stirred at ambient temperature for 15min until the evolution of gas had ceased. Then4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(1.00 g, 2.07 mmol) was added and the mixture stirred at 70° C. for 3 h.After cooling to ambient temperature 5 M formic acid (1.2 ml, 6.2 mmol)and water were added and the mixture extracted two times with ethylacetate. The combined organic phases were dried and evaporated underreduced pressure. The residue was purified by column chromatography onsilica (100 g) with cyclohexane/ethyl acetate (5-50%).

Yield: 650 mg (96% purity, 54% of th.)

LC-MS (Method L6): R_(f)=2.46 min; MS (ESIpos): m/z=560 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (3.55), 0.008 (3.23),0.146 (0.40), 0.890 (0.44), 1.157 (2.49), 1.175 (7.53), 1.188 (4.41),1.193 (9.23), 1.205 (8.20), 1.211 (4.25), 1.215 (2.56), 1.223 (4.21),1.233 (2.01), 1.245 (1.50), 1.250 (2.12), 1.264 (0.77), 1.268 (1.05),1.988 (9.00), 2.083 (0.45), 2.092 (0.48), 2.104 (0.46), 2.116 (0.65),2.129 (0.70), 2.163 (1.14), 2.176 (1.60), 2.187 (1.26), 2.327 (0.47),2.366 (0.41), 2.523 (1.67), 2.669 (0.54), 2.710 (0.46), 3.998 (2.03),4.002 (0.89), 4.021 (2.14), 4.038 (2.14), 4.056 (0.79), 4.133 (0.51),4.151 (0.98), 4.168 (0.93), 4.175 (0.83), 4.186 (0.84), 4.193 (1.11),4.202 (2.21), 4.210 (1.51), 4.219 (4.66), 4.228 (3.20), 4.236 (4.66),4.246 (3.73), 4.254 (2.15), 4.263 (1.53), 4.272 (0.85), 4.287 (1.21),4.298 (1.72), 4.309 (1.16), 5.226 (0.78), 5.245 (0.83), 5.266 (0.79),5.285 (0.73), 6.794 (1.56), 6.804 (5.05), 6.815 (1.91), 6.826 (4.30),6.837 (0.92), 6.856 (1.42), 6.866 (0.52), 6.875 (0.87), 6.917 (0.71),6.936 (1.45), 6.955 (0.86), 7.142 (0.96), 7.145 (0.95), 7.163 (1.28),7.173 (0.83), 7.177 (0.93), 7.194 (1.20), 7.212 (0.58), 7.387 (1.34),7.408 (1.79), 7.429 (1.14), 7.599 (0.99), 7.603 (1.04), 7.683 (16.00),7.702 (0.43), 7.875 (1.05), 7.879 (1.00), 7.897 (2.37), 7.914 (1.62),7.918 (1.55), 8.002 (3.30), 8.019 (2.41), 8.408 (1.18), 8.423 (1.48),8.443 (1.15), 9.112 (4.72), 9.124 (4.29), 9.517 (1.49), 9.525 (1.44),9.537 (1.51), 9.544 (1.34).

Synthesis of4-(cyanomethyl)-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(Example 355)

A solution of ethylcyano{8-(3,5-dichlorophenyl)-3-[(4S)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]quinolin-4-yl}acetate(example 354) (300 mg, 0.54 mmol) in DMSO (2.4 ml) was treated withsodium chloride (63 mg, 1.1 mmol) and water (0.24 ml) and heated understirring overnight at 90° C. Water (2.5 ml) was added, the precipitatefiltered off, washed with water and dried in vacuo.

Yield: 250 mg (99% purity, 95% of th.)

LC-MS (Method L1): R_(f)=1.24 min; MS (ESIpos): m/z=488 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: 2.099 (0.43), 2.136 (0.80),2.145 (0.69), 2.205 (0.64), 2.224 (0.67), 2.239 (0.54), 4.266 (1.68),4.277 (2.29), 4.711 (6.99), 5.278 (0.45), 5.294 (1.03), 5.312 (1.04),5.326 (0.45), 6.798 (2.04), 6.818 (2.30), 6.899 (1.01), 6.917 (2.07),6.936 (1.19), 7.163 (1.04), 7.182 (1.68), 7.200 (0.79), 7.387 (1.76),7.405 (1.62), 7.677 (16.00), 7.883 (1.06), 7.903 (1.92), 7.922 (1.56),7.988 (2.46), 8.006 (1.65), 8.417 (1.93), 8.437 (1.73), 9.029 (5.73),9.379 (1.69), 9.399 (1.68).

Synthesis of4-(2-amino-2-oxoethyl)-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(Example 360)

A suspension of4-(cyanomethyl)-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(example 355) (150 mg, 307 μmol) in conc. hydrochloric acid (0.77 ml,37%) and dioxan (0.5 ml) was stirred 3 days at ambient temperature. Thesolid was filtered off, washed with dioxan and dried in vacuo.

Yield: 90 mg (92% purity, 53% of th.)

LC-MS (Method L1): R_(f)=1.13 min; MS (ESIpos): m/z=506 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.149 (0.40), 0.008 (3.42),2.068 (0.55), 2.085 (0.61), 2.095 (0.80), 2.208 (0.74), 2.220 (0.70),2.229 (0.68), 2.242 (0.51), 2.327 (0.61), 2.366 (0.61), 2.670 (0.57),2.710 (0.54), 2.794 (0.77), 3.568 (2.60), 4.179 (0.56), 4.197 (0.56),4.216 (3.94), 4.225 (3.86), 4.238 (1.19), 4.264 (1.32), 4.283 (1.00),5.270 (0.46), 5.285 (1.06), 5.304 (1.07), 5.319 (0.51), 6.779 (1.94),6.800 (2.15), 6.883 (0.98), 6.899 (2.02), 6.918 (1.20), 7.147 (1.02),7.164 (1.67), 7.185 (0.81), 7.349 (2.28), 7.369 (1.67), 7.659 (16.00),7.764 (1.23), 7.782 (1.93), 7.803 (1.67), 7.894 (2.35), 7.910 (1.74),7.989 (1.55), 8.349 (1.83), 8.368 (1.68), 8.949 (6.32), 9.468 (1.76),9.488 (1.75).

The filtrate was adjusted to pH 6 by addition of aqueoussodiumbicarbonate (7 ml, 1.5 M) and extracted with ethyl acetate. Thecombined organic phases were dried, evaporated and the residue purifiedby prep. HPLC (C18, gradient: 0.1% aq. formic acid/acetonitrile)yielding a second crop (40 mg, 100% purity, 26% of th.)

Synthesis of4-cyano-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(Example 362)

Under argon atmosphere a thick-walled microwave vessel was charged with4-chloro-8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]quinoline-3-carboxamide(1.00 g, 2.07 mmol), copper(I)cyanide (185 mg, 2.07 mmol),sodiumcarbonate (219 mg, 2.07 mmol),1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (169 mg, 0.21 mmol) and N-methyl pyrrolidon (7.2ml), capped and heated overnight under stirring at 120° C. The reactionmixture was added to a 3:1 mixture of saturated aq.ammoniumchloride/conc. aqueous ammonia (120 ml) and ethyl acetate,stirred for 30 min and filtered through celite. The phases wereseparated, the organic phase washed three times with a 3:1 mixture ofsaturated aq. ammoniumchloride/conc. aq. ammonia, then brine and dried.The residue (1.06 g) was purified by column chromatography on silica(100 g) with cyclohexane/ethyl acetate (3-30%).

Yield: 760 mg (93% purity, 72% of th.)

LC-MS (Method L1): R_(f)=1.44 min; MS (ESIpos): m/z=474 [M+H]⁺

¹H-NMR Peaklist (400 MHz, DMSO-d6) δ[ppm]: −0.008 (0.70), 0.008 (0.49),1.398 (16.00), 1.988 (0.45), 2.519 (0.43), 6.790 (0.48), 6.849 (0.44),6.851 (0.45), 6.870 (0.51), 6.872 (0.48), 6.966 (0.40), 7.673 (0.41),7.696 (4.12), 7.933 (0.43), 7.951 (0.60), 7.953 (0.54), 7.972 (0.53),8.054 (0.67), 8.057 (0.62), 8.071 (0.49), 8.075 (0.41), 9.279 (0.96),9.311 (0.50).

Synthesis of8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-2-methylquinoline-3-carboxamide(Example 481)

Step 1

tert-butyl 8-bromo-4-hydroxy-2-methylquinoline-3-carboxylate

A three-necked flask was charged with sodium hydride (910 mg, 22.7 mmol,60% dispersion in mineral oil) and dry DMF (50 mL). 3-Bromoisatoicanhydride (5 g, 20.6 mmol) was added slowly (0.42 g, 4 mmol), followedby dropwise addition of tert-butyl 3-oxobutanoate (3.6 g, 22.7 mmol)dissolved in 50 mL DMF at room temperature. The reaction mixture washeated to 120° C. for 10 minutes. Then the solvent was removed underreduced pressure and the remaining material was dispersed in water andextracted twice with dichloromethane. The combined organic layers weredried over sodium sulfate, filtered and reduced in vacuo. The resultingresidue was purified by silica gel flash chromatography (eluentcyclohexane/ethyl acetate gradient).

Yield: 1.05 g (2.96 mmol, 15% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 10.48 (s, 1H), 8.10-8.08 (d, 1H), 8.02-7.99(d, 1H), 7.31-7.27 (t, 1H), methyl singulett under DMSO signal, 1.51 (s,9H).

Step 2

8-bromo-4-chloro-2-methylquinoline-3-carbonyl chloride

A three-necked flask was charged with tert-butyl8-bromo-4-hydroxy-2-methylquinoline-3-carboxylate (1.2 g, 3.54 mmol))and phosphorus oxychloride (42 g, 274 mmol) and heated to reflux for 16h. The reaction mixture was reduced in vacuo and used as such in thenext step.

Step 3

8-bromo-4-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-2-methylquinoline-3-carboxamide

8-Bromo-4-chloro-2-methylquinoline-3-carbonyl chloride (raw product fromstep 2) (1 g, 3.13 mmol) was dissolved in 60 mL acetonitril and mixedwith (4S)-chroman-4-amine hydrochloride (582 mg, 3.13 mmol) andtriethylamine (951 mg, 9.4 mmol) at 0° C. The reaction mixture wasallowed to warm to room temperature and stirred until completeconversion. The solvent was removed under reduced pressure; theremaining solution was extracted twice with dichloromethane. Thecombined organic layers were dried over sodium sulfate, filtered andreduced in vacuo. The resulting residue was purified by silica gel flashchromatography (eluent cyclohexane/ethyl acetate gradient).

Yield: 766 mg (1.77 mmol, 55% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 9.29 (d, 1H, NH), 8.26-8.22 (t, 2H),7.66-7.62 (dd, 1H), 7.38 7.36 (d, 1H), 7.20-7.16 (t, 1H), 6.97-6.93 (t,1H), 6.82-6.80 (d, 1H), 5.32-5.28 (m, 1H), 4.34-4.29 (m, 1H), 4.23-4.17(m, 1H), 2.71 (s, 3H), 2.28-2.22 (m, 1H), 2.10-2.03 (m, 1H).

Step 4

8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-2-methylquinoline-3-carboxamide

8-Bromo-4-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-2-methylquinoline-3-carboxamide(step 3) (766 mg, 1.77 mmol) in 30 mL dioxane were distributed to threemicrowave flasks (20 mL volume). Each of it was charged with 3.7 mLaqueous dimethylamine solution (40%, combined 8.87 mmol). The reactionmixtures were heated in a microwave oven (Anton Paars Monowave 400) to100° C. for 40 minutes. The reaction mixtures were combined and thesolvent was removed under reduced pressure. The resulting residue waspurified by silica gel flash chromatography (eluent cyclohexane/ethylacetate gradient).

Yield: 625 mg (1.42 mmol, 73% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 9.07 (d, 1H, NH), 8.08-8.02 (2d, 2H),7.41-7.37 (t, 1H), 7.32 7.31 (d, 1H), 7.20-7.16 (t, 1H), 6.96-6.92 (t,1H), 6.82-6.79 (d, 1H), 5.28-5.26 (m, 1H), 4.35-4.27 (m, 1H), 4.23-4.16(m, 1H), 3.01 (s, 6H), 2.61 (s, 3H), 2.28-2.19 (m, 1H), 2.10-2.02 (m,1H).

Step 5

8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-2-methylquinoline-3-carboxamide(Example 481)

To a degassed (1 min, argon) mixture of8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-2-methylquinoline-3-carboxamide(step 4) (200 mg, 0.45 mmol), (2,3-dichlorophenyl)boronic acid (130 mg,0.68 mmol), potassium carbonate (125.5 mg, 0.90 mmol), water (3.5 mL)and dioxane (12 mL) was added1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (18.5 mg,0.02 mmol). The reaction mixture was stirred for 16 h at 85° C., thencooled down to room temperature, diluted with water and extracted twicewith dichloromethane. The combined organic layers were dried over sodiumsulfate, filtered and reduced in vacuo. The resulting residue waspurified by silica gel flash chromatography (eluent cyclohexane/ethylacetate gradient) to obtain the title compound.

Yield: 159 mg (0.31 mmol, 66% of th.)

¹H-NMR (400 MHz, DMSO-d6) δ 9.06 (d, 1H, NH), 8.17-8.15 (d, 1H),7.68-7.66 (d, 1H), 7.58-7.55 (m, 2H), 7.42-7.42 (m, 1H), 7.32-7.30 (m,2H), 7.17-7.15 (t, 1H), 6.93-6.91 (t, 1H), 6.80-6.78 (d, 1H), 5.28-5.24(m, 1H), 4.32-4.27 (m, 1H), 4.23-4.17 (m, 1H), 3.04 (s, 6H), methylsingulett under DMSO signal, 2.24-2.18 (m, 1H), 2.08-2.02 (m, 1H).

Synthesis of8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(tetrahydro-2H-pyran-4-yl)quinoline-3-carboxamide(Example 539)

Under argon atmosphere8-(3,5-dichlorphenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(3,6-dihydro-2H-pyran-4-yl)chinolin-3-carboxamide(60.0 mg, 113 μmol) was dissolved in ethyl acetate/ethanol (2:1, 6 ml).The catalyst, 10% palladium on charcoal (20 mg), was added, argonreplaced by hydrogen and the mixture stirred under atmospheric pressureof hydrogen for 4.5 h. More 10% palladium on charcoal (20 mg) was addedunder argon and hydrogenation continued under atmospheric pressure for 6h. The reaction mixture was filtered over celite, rinsed with ethylacetate and concentrated in vacuo. The residue (66 mg) was purified byprep. HPLC (C18, gradient: 0.1% aq. formic acid/acetonitrile).

Yield: 11 mg (18% of th.)

LC-MS (Method L1): Rt=1.28 min; MS (ESIpos): m/z=533 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: 0.008 (2.51), 1.235 (0.43), 1.676(1.54), 1.713 (2.60), 1.751 (1.67), 2.057 (0.97), 2.072 (1.11), 2.085(1.87), 2.218 (1.33), 2.231 (1.31), 2.240 (1.26), 2.252 (0.92), 2.327(0.56), 2.366 (0.60), 2.429 (2.14), 2.460 (2.25), 2.670 (0.69), 2.710(0.67), 3.464 (1.07), 3.493 (1.97), 3.520 (2.14), 3.546 (2.15), 3.575(1.18), 3.738 (1.26), 4.010 (3.17), 4.023 (2.81), 4.038 (2.85), 4.219(0.82), 4.240 (2.21), 4.247 (1.78), 4.260 (2.15), 4.268 (2.70), 4.279(2.21), 4.295 (1.97), 5.293 (0.94), 5.307 (2.08), 5.327 (2.08), 5.342(0.90), 5.754 (5.00), 6.785 (3.97), 6.804 (4.38), 6.918 (1.97), 6.937(4.07), 6.956 (2.40), 7.158 (2.10), 7.176 (3.37), 7.193 (1.61), 7.405(3.52), 7.423 (3.20), 7.613 (13.15), 7.617 (16.00), 7.648 (4.20), 7.653(5.68), 7.748 (2.29), 7.766 (3.65), 7.787 (3.20), 7.856 (4.95), 7.874(3.52), 8.510 (3.43), 8.531 (3.17), 8.777 (12.63), 9.140 (3.54), 9.161(3.54).

Synthesis ofN-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(methoxymethyl)-8-(2,3,5-trifluorophenyl)quinoline-3-carboxamide(Example 686)

Step 1

ethyl 8-bromo-4-methylquinoline-3-carboxylate

To a solution of ethyl 8-bromo-4-hydroxy-quinoline-3-carboxylate (3.00g, 9.54 mmol) (Gharat, al., WO 2013/118071) in THF (45 ml) was addedunder argon cobalt(II)acetylacetonate (2.45 g, 9.54 mmol). The mixturewas warmed in an oil bath of 60° C., dimethylzink (solution in toluene,1.9 ml, 2.0 M, 3.8 mmol) was added dropwise and stirred at thistemperature for 1 h. During a period of 4.5 h more dimethylzink(solution in toluene, 6.2 ml, 2.0 M, 12.4 mmol) was added at thistemperature in several portions until almost all starting material wasconsumed (HPLC monitoring). The mixture was poured into water (250 ml),containing acetic acid (1.8 ml), the organic solvents largely evaporatedunder diminished pressure and the aqueous phase extracted withethylacetate. The combined organic phases were dried and evaporated todryness. The residue (3.1 g) was purified by column chromatography onsilica (100 g), eluent: cyclohexane/ethyl acetate (3-10%) yielding thetitel compound (1.25 g, 45% of theory)

LC-MS (Method L4): R_(f)=3.06 min; MS (ESIpos): m/z=294 [M+H]⁺

¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: 1.369 (4.76), 1.387 (9.98), 1.405(4.89), 2.934 (16.00), 4.393 (1.57), 4.411 (4.77), 4.429 (4.71), 4.447(1.51), 7.615 (1.30), 7.634 (2.23), 7.655 (1.46), 8.253 (1.85), 8.271(1.76), 8.340 (2.09), 8.361 (1.99), 9.185 (3.32).

Step 2

ethyl 8-bromo-4-(bromomethyl)quinoline-3-carboxylate

Ethyl-8-bromo-4-methylquinoline-3-carboxylate (1.50 g, 5.10 mmol) wasdissolved in THF (23 ml). Phenyltrimethylammonium tribromide (3.07 g,8.16 mmol) and acetic acid (1.5 ml, 25 mmol) were added and the mixturestirred at ambient temperature.

More phenyltrimethylammonium tribromide (0.96 g, 2.5 mmol) was added andstirred for 3 d at ambient temperature. Another portion ofphenyltrimethylammonium tribromide (0.96 g, 2.5 mmol) and acetic acid(0.9 ml, 15.3 mmol) were added and stirring continued overnight. Thereaction mixture was diluted with water and dichloromethane. The aqueousphase was extracted with dichloromethane and the combined organic layerswere washed with an aqueous sodium hydrogencarbonate solution, dried andconcentrated in vacuo at 30° C.

The residue was stirred for 1 h in MTBE (80 ml). The solid was filteredoff, washed with MTBE and dried in vacuo. The crude (3.23 g) waspurified by column chromatography, eluent cyclohexane/ethyl acetate(3-22%).

Yield: 985 mg (90.5% purity, 47% of th.)

LC-MS (Method L1): R_(f)=1.11 min; MS (ESIpos): m/z=371 [M+H]⁺

¹H-NMR (500 MHz, DMSO-d6) δ[ppm]: 1.401 (7.41), 1.415 (16.00), 1.429(7.42), 1.435 (0.41), 4.441 (2.26), 4.455 (7.12), 4.470 (6.98), 4.484(2.13), 5.479 (11.96), 5.758 (1.31), 7.721 (2.28), 7.736 (2.76), 7.738(2.62), 7.753 (2.43), 8.311 (2.94), 8.314 (3.02), 8.326 (2.85), 8.329(2.69), 8.446 (2.62), 8.448 (2.54), 8.463 (2.57), 8.465 (2.29), 9.311(8.57).

Step 3

8-bromo-4-(methoxymethyl)quinoline-3-carboxylic acid

A suspension of ethyl 8-bromo-4-(bromomethyl)quinoline-3-carboxylate(1.14 g, 3.06 mmol) in methanol (15 ml) was treated dropwise with sodiummethoxide (solution in methanol, 5.4 M) at ambient temperature duringwhich dissolution occurred and later a solid precipitated. After 1.5 hTHF (5 ml) and water (3 ml) were added and stirring continued over nightat ambient temperature. The solution was then diluted with 20 mL ofwater and the pH was adjusted to 4 by addition of acetic acid (5 M).After concentration in vacuo to remove most of the organic solvents theremaining mixture was distributed between ethyl acetate and water. Theaqueous layer was extracted several times with ethyl acetate and thecombined organic layers were dried and concentrated in vacuo. Thismaterial (363 mg, 91% purity, 37% of theory) was suitable for furtheruse. The aqueous phase war concentrated to a small volume under reducedpressure, diluted with DMSO and purified by prep. HPLC (C18, gradient:0.1% aq. formic acid/acetonitrile) yielding a second crop (270 mg, 100%purity, 30% of theory).

LC-MS (Method L1): R_(f)=0.69 min; MS (ESIpos): m/z=296 [M+H]⁺

¹H-NMR (500 MHz, DMSO-d6) δ[ppm]: 1.221 (0.47), 3.184 (0.52), 5.199(16.00), 7.611 (3.54), 7.627 (5.28), 7.643 (3.76), 8.238 (4.81), 8.252(4.56), 8.351 (4.61), 8.367 (4.38), 9.215 (10.02).

Step 4

8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(methoxymethyl)quinoline-3-carboxamide

A solution of 8-bromo-4-(methoxymethyl)quinoline-3-carboxylic acid (360mg, 1.22 mmol) in THF (6 ml) was treated with (4S)-chroman-4-aminehydrochloride (1:1) and trimethylamine (680 μl, 4.9 mmol). The mixturewas warmed to 45° C., 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane2,4,6-trioxide (solution in ethyl acetate, 23 ml, 50% content, 39 mmol)was added, the heating removed and the mixture stirred at ambienttemperature overnight. After dilution with water (pH 8-9) the THF wasremoved in vacuo. The precipitate was filtered off and dissolved inapprox. 10 ml of warm acetone. Warm water was added (10 mL) and themixture was allowed to cool to RT. The solid was filtered off, washedwith acetone/water (1:2) and dried in vacuo.

Yield: 391 mg (95% purity, 72% of th.)

LC-MS (Method L1): R_(f)=0.96 min; MS (ESIpos): m/z=427 [M+H]⁺

¹H-NMR (600 MHz, DMSO-d6) δ[ppm]: 1.235 (0.52), 2.090 (2.20), 2.230(2.15), 3.287 (16.00), 4.241 (2.66), 4.293 (2.83), 4.998 (8.92), 5.314(2.68), 6.800 (2.83), 6.811 (3.13), 6.943 (3.04), 7.183 (3.03), 7.397(3.01), 7.612 (3.03), 8.211 (2.99), 8.221 (3.08), 8.311 (2.87), 8.324(2.94), 8.998 (4.49), 9.207 (2.80).

Step 5

N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(methoxymethyl)-8-(2,3,5-trifluorophenyl)quinoline-3-carboxamide(Example 686)

Under argon a vessel was charged with8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(methoxymethyl)quinoline-3-carboxamide(90 mg, 211 μmol), 2,3,5-trifluorobenzene boronic acid (55.6 mg, 316μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (8.60 mg, 10.5 μmol), potassium carbonate (58.2mg, 421 μmol) and with a degassed 5:1 mixture of dioxan and water (0.73ml). The mixture was stirred overnight at 70° C. It was diluted withethyl acetate, filtered through a sodium sulfate plug and concentratedin vacuo. The crude was purified by prep. HPLC (C18, gradient: 0.1% aq.formic acid/acetonitrile.

Yield: 31 mg (31% of th.)

LC-MS (Method L1): R_(f)=1.14 min; MS (ESIpos): m/z=479 [M+H]⁺

¹H-NMR (600 MHz, DMSO-d6) δ[ppm]: 0.005 (1.04), 2.043 (0.47), 2.048(0.60), 2.053 (0.96), 2.058 (1.04), 2.065 (1.12), 2.069 (1.07), 2.077(1.37), 2.081 (1.20), 2.087 (2.11), 2.092 (0.63), 2.193 (0.58), 2.199(0.86), 2.202 (0.81), 2.207 (1.32), 2.213 (0.97), 2.216 (1.31), 2.221(1.32), 2.230 (0.99), 2.236 (0.64), 2.239 (0.62), 2.244 (0.46), 2.793(0.55), 3.345 (8.00), 4.220 (0.71), 4.225 (0.87), 4.234 (0.90), 4.239(2.32), 4.244 (1.61), 4.253 (1.77), 4.258 (1.47), 4.268 (1.42), 4.273(1.80), 4.279 (1.58), 4.285 (1.91), 4.292 (0.78), 4.298 (0.84), 4.303(0.65), 5.037 (16.00), 5.287 (0.91), 5.297 (1.95), 5.310 (1.96), 5.320(0.92), 6.790 (3.66), 6.791 (3.76), 6.803 (4.00), 6.804 (3.99), 6.917(1.85), 6.918 (1.84), 6.929 (3.75), 6.931 (3.68), 6.942 (2.14), 6.943(2.05), 7.159 (1.78), 7.161 (1.80), 7.173 (3.01), 7.184 (1.56), 7.187(1.49), 7.259 (1.51), 7.267 (1.49), 7.274 (1.49), 7.376 (3.08), 7.388(2.95), 7.609 (0.49), 7.614 (0.63), 7.619 (0.75), 7.624 (1.18), 7.628(1.14), 7.633 (1.23), 7.638 (1.18), 7.642 (1.18), 7.646 (0.74), 7.651(0.65), 7.657 (0.56), 7.800 (2.66), 7.812 (3.85), 7.814 (3.18), 7.826(3.61), 7.873 (4.17), 7.875 (4.29), 7.885 (3.06), 7.887 (2.94), 8.416(3.61), 8.418 (3.65), 8.430 (3.48), 8.432 (3.27), 8.890 (12.74), 9.184(3.52), 9.197 (3.43).

Synthesis ofN-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(oxetan-3-yl)-8-(2,3,5-trifluorophenyl)quinoline-3-carboxamide(Example 660)

In a 100 mL round bottom flask, a mixture of4-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-8-(2,3,5-trifluorophenyl)quinoline-3-carboxamide(500 mg, 1.066 mmol), anhydrous lithium hydroxide (51 mg, 2.133 mmol),3-bromooxetane (0.133 mL, 1.600 mmol),[4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate (24 mg, 0.021 mmol) andtris(trimethylsilyl)silane (0.329 mL, 1.066 mmol) in 1,2-dimethoxyethane(20 mL) was degassed by purging with argon. In a 50 mL round bottomflask, a mixture of nickel(II) chloride ethylene glycol dimethyl ethercomplex (14 mg, 0.064 mmol) and 4,4′-di-tert-butyl-2,2′-bipyridine (17mg, 0.064 mmol) in 1,2-dimethoxyethane (10 mL) was gently warmed with aheatgun, purged with argon and stirred for five minutes. By syringe halfof this nickel-catalyst mixture (5 mL) was added to the reactionmixture. The resulting suspension was purged with argon for five minutesand was subsequently stirred under irradiation with blue LED light for18 h while cooling with a fan. The reaction mixture was diluted withdichloromethane (30 mL). Water (10 mL) was added and the layers wereseparated. The aqueous layer was extracted with dichloromethane (2×10mL). Combined organic layers were dried with sodium sulfate and solventswere removed in vacuo. Purification by flash column chromatography (80g; heptane, 10%-60% ethyl acetate) and preparative HPLC (Method 11)afforded 0.054 g (0.110 mmol; 10% of theory) of the title compound.

LC-MS (Method 2): R_(f)=3.65 min; m/z=491 (M+H)⁺

¹H-NMR (400 MHz, DMSO-d₆) δ 9.26 (d, J=8.1 Hz, 1H), 8.87 (s, 1H),7.91-7.87 (m, 1H), 7.84-7.73 (m, 2H), 7.70-7.57 (m, 1H), 7.35 (d, J=7.8Hz, 1H), 7.30-7.23 (m, 1H), 7.19 (t, J=7.8 Hz, 1H), 6.93 (t, J=7.5 Hz,1H), 6.81 (d, J=8.2 Hz, 1H), 5.31-5.11 (m, 4H), 4.84-4.70 (m, 2H),4.34-4.21 (m, 2H), 2.25-2.15 (m, 1H), 2.08-2.01 (m, 1H).

TABLE 1 Examples (I)

Number R1 R2 R3 R4 R5 R6 Q A 1 H chloro H H H H 3,5- (1S)-1,2,3,4-dimethylphenyl tetrahydronaphth- alen-1-yl 2 H chloro H H H H 3,5-(1S)-1,2,3,4- dichlorophenyl tetrahydronaphth- alen-1-yl 3 H chloro H HH H 3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 4 H chloro H H HH 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 5 H chloro H H HH 3-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 6 H chloro H H H H3-chlorophenyl (1S)-2,3-dihydro- 1H-inden-1-yl 7 H chloro H H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 8 H dimethylamino H H HH 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 9 Hdimethylamino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 10 H dimethylamino H H H H 2-chloro-6- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 11 H dimethylamino H H methyl H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 12 H dimethylamino H Hmethyl H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 13 Hdimethylamino H H H H 3,5-dichloro-4- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 14 H pyrrolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 15 H dimethylamino H H H H 3,5-(4S)-3,4-dihydro- dimethylphenyl 2H-chromen-4-yl 16 H dimethylamino H HH H 3,5- (1S)-1,2,3,4- dichlorophenyl tetrahydronaphth- alen-1-yl 17 Hmorpholin-4-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 18 H dimethylamino H methyl H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 19 H dimethylamino H methyl H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 20 H morpholin-4-yl H H HH 3,5- (1S)-1,2,3,4- dichlorophenyl tetrahydronaphth- alen-1-yl 21 Hdimethylamino H fluoro H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 22 H dimethylamino H fluoro H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 23 H methylamino H H H H 3,5-dichloro-4-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 24 H methylamino H H H H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 25 Hmorpholin-4-yl H H H H 3-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl26 H 1H-imidazol-1-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 27 H (1S)-2,3-dihydro-1H-inden-1- H H H H 3-chlorophenyl(1S)-2,3-dihydro- ylamino 1H-inden-1-yl 28 H(1S)-2,3-dihydro-1H-inden-1- H H H H 2,3- (1S)-2,3-dihydro- ylaminodichlorophenyl 1H-inden-1-yl 29 H dimethylamino H H H H 2-chloro-5-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 30 H dimethylamino H H HH 3,4- (4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 31 Hdimethylamino H H H H 4-fluoro-3- (4S)-3,4-dihydro- methoxyphenyl2H-chromen-4-yl 32 H dimethylamino H H H H 2,4-difluoro-3-(4S)-3,4-dihydro- methoxyphenyl 2H-chromen-4-yl 33 H dimethylamino H H HH 3-fluoro-2- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 34 Hdimethylamino H H H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 35 H morpholin-4-yl H H H H 3-chlorophenyl(1S)-2,3-dihydro- 1H-inden-1-yl 36 H dimethylamino H H H H 3-chloro-2-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 37 H dimethylamino H H HH 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 38 Hdimethylamino H H H H 2,4,6-trifluoro-3- (4S)-3,4-dihydro- methoxyphenyl2H-chromen-4-yl 39 H dimethylamino H H H H 3-chloro-5- (4S)-3,4-dihydro-(trifluoromethyl) 2H-chromen-4-yl phenyl 40 H dimethylamino H H fluoro H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 41 H dimethylaminoH H fluoro H 3,5-dichloro-4- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 42 H morpholin-4-yl H H fluoro H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 43 H morpholin-4-yl H H fluoro H3,5-dichloro-4- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 44 Hdimethylamino H H H H 3-chloro-5- (4S)-3,4-dihydro- methylphenyl2H-chromen-4-yl 45 H dimethylamino H H H H 3-chloro-4- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 46 H dimethylamino H H H H 3-chloro-5-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 47 H dimethylamino H H HH 3,4,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 48 Hdimethylamino H H H H 2-fluoro-3- (4S)-3,4-dihydro- (trifluoromethoxy)2H-chromen-4-yl yl)phenyl 49 H dimethylamino H H H H 3,5-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 50 H dimethylamino H HH H 2-fluoro-3- (4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-ylphenyl 51 H dimethylamino H H H H 3-chloro-2- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 52 H morpholin-4-yl H H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 53 H morpholin-4-yl H HH H 2,4-difluoro-3- (4S)-3,4-dihydro- methoxyphenyl 2H-chromen-4-yl 54 Hmorpholin-4-yl H H H H 3,5-dichloro-4- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 55 H dimethylamino H H H H 3-fluoro-4- (4S)-3,4-dihydro-methoxyphenyl 2H-chromen-4-yl 56 H dimethylamino H H H H 3-chloro-4-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 57 H dimethylamino H H HH 2,4,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 58 H amino HH H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 59 Hbenzyl(methyl)amino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 60 H dimethylamino H H H H 2-chloro-3- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 61 H dimethylamino H H H H 3-fluoro-5-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 62 H dimethylamino H H HH 3-fluoropyridin- (4S)-3,4-dihydro- 2-yl 2H-chromen-4-yl 63 Hdimethylamino H H H H 2-fluoropyridin- (4S)-3,4-dihydro- 4-yl2H-chromen-4-yl 64 H dimethylamino H H H H 2- (4S)-3,4-dihydro-methoxypyridin- 2H-chromen-4-yl 4-yl 65 H dimethylamino H H H H2-chloropyridin- (4S)-3,4-dihydro- 4-yl 2H-chromen-4-yl 66 Hdimethylamino H H H H 2,6- (4S)-3,4-dihydro- dimethylpyridin-2H-chromen-4-yl 4-yl 67 H diethylamino H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 68 H 4-(trifluoromethyl)-1H- H H H H 3,5-(4S)-3,4-dihydro- pyrazol-1-yl dichlorophenyl 2H-chromen-4-yl 69 H1H-pyrazol-4-ylamino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 70 H dimethylamino H H H H 3- (4S)-3,4-dihydro-(dimethylamino) 2H-chromen-4-yl phenyl 71 H dimethylamino H H H H1-methyl-1H- (4S)-3,4-dihydro- benzimidazol-6- 2H-chromen-4-yl yl 72 H1H-pyrazol-1-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 73 H dimethylamino H H H H 1H-indol-4-yl(4S)-3,4-dihydro- 2H-chromen-4-yl 74 H (2-hydroxyethyl)amino H H H H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 75 H (2- H H H H3,5- (4S)-3,4-dihydro- methoxyethyl)(methyl)amino dichlorophenyl2H-chromen-4-yl 76 H (2-methoxyethyl)amino H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 77 H4-oxoimidazolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 78 H bis(2-methoxyethyl)amino H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 79 H pyrrolidin-1-yl HH H H 3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 80 H(2S)-2-carboxypyrrolidin-1-yl H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 81 H dimethylamino H H H H 2,3,4-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 82 H morpholin-4-yl HH H H 2,3,4- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 83 Hmorpholin-4-yl H H H H 2-fluoro-3- (4S)-3,4-dihydro- (trifluoromethoxy)2H-chromen-4-yl phenyl 84 H (3R)-3-aminopyrrolidin-1-yl H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 85 H3,4-dihydroisoquinolin-2(1H)- H H H H 3,5- (1S)-2,3-dihydro- yldichlorophenyl 1H-inden-1-yl 86 H anilino H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 87 H isobutyl(methyl)amino H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 88 H [2- H H H H 3,5-(1S)-2,3-dihydro- (dimethylamino)ethyl]amino dichlorophenyl1H-inden-1-yl 89 H (2-methoxyethyl)amino H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 90 H ethyl(2-methoxyethyl)amino H H H H3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 91 H (2S)-2- H H H H3,5- (1S)-2,3-dihydro- (methoxymethyl)pyrrolidin-1- dichlorophenyl1H-inden-1-yl yl 92 H (2R)-2- H H H H 3,5- (1S)-2,3-dihydro-(methoxymethyl)pyrrolidin-1- dichlorophenyl 1H-inden-1-yl yl 93 Hbis(2-methoxyethyl)amino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 94 H (3S)-3- H H H H 3,5- (1S)-2,3-dihydro-(dimethylamino)pyrrolidin-1- dichlorophenyl 1H-inden-1-yl yl 95 Htetrahydro-2H-pyran-4- H H H H 3,5- (1S)-2,3-dihydro- ylaminodichlorophenyl 1H-inden-1-yl 96 H [2-(pyrrolidin-1-yl)ethyl]amino H H HH 3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 97 H(3,3,3-trifluoropropyl)amino H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 98 H morpholin-4-ylamino H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 99-1 H(pyridin-2-ylmethyl)amino) H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 99-2 H [(2R)-1-hydroxybutan-2- H H H H 3,5-(1S)-2,3-dihydro- yl]amino dichlorophenyl 1H-inden-1-yl 100 H(2-hydroxyethyl)amino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 101 H (3R)-3-hydroxypyrrolidin-1-yl H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 102 H3-hydroxyazetidin-1-yl H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 103 H 3-(pyrrolidin-1-yl)azetidin-1-yl H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 104 Hcyclopropyl(ethyl)amino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 105 H cyclobutyl(methyl)amino H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 106 H(cyclopropylmethyl)(methyl)a- H H H H 3,5- (1S)-2,3-dihydro- minodichlorophenyl 1H-inden-1-yl 107 H 2,2-dimethylmorpholin-4-yl H H H H3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 108 H1,2-oxazolidin-2-yl H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 109 H (2S)-2-methyl-2,3-dihydro- H H H H 3,5-(1S)-2,3-dihydro- 1H-indol-1-yl dichlorophenyl 1H-inden-1-yl 110 Hmethyl(2,2,2- H H H H 3,5- (1S)-2,3-dihydro- trifluoroethyl)aminodichlorophenyl 1H-inden-1-yl 111 H 1,3-dihydro-2H-isoindol-2-yl H H H H3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 112 H3,3-difluoropyrrolidin-1-yl H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 113 H (2S)-2-carbamoylpyrrolidin-1- H H H H3,5- (1S)-2,3-dihydro- yl dichlorophenyl 1H-inden-1-yl 114 Hmethyl(1-phenylethyl)amino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 115 H (3-amino-3- H H H H 3,5- (1S)-2,3-dihydro-oxopropyl)(methyl)amino dichlorophenyl 1H-inden-1-yl 116 H4-acetylpiperazin-1-yl H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 117 H 1,1-dioxidothiomorpholin-4-yl H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 118 H benzyl(methyl)aminoH H H H 3,5- (1S)-2,3-dihydro dichlorophenyl 1H-inden-1-yl 119 H3-fluoroazetidin-1-yl H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 120 H 3-methylazetidin-1-yl H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 121 H 3,3-difluoroazetidin-1-yl H H H H3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 122 H[3-(dimethylamino)-3- H H H H 3,5- (1S)-2,3-dihydro- oxopropyl]aminodichlorophenyl 1H-inden-1-yl 123 H [(5-methyl-1,2,4-oxadiazol-3- H H H H3,5- (1S)-2,3-dihydro- yl)methyl]amino dichlorophenyl 1H-inden-1-yl 124H (3-amino-3-oxopropyl)amino H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 125 H [2-(1H-pyrazol-1- H H H H 3,5-(1S)-2,3-dihydro yl)ethyl]amino dichlorophenyl 1H-inden-1-yl 126 H(2-acetamidoethyl)amino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 127 H [(2S)-1-amino-1-oxopropan- H H H H 3,5-(1S)-2,3-dihydro- 2-yl]amino dichlorophenyl 1H-inden-1-yl 128 H(2-methoxy-2-oxoethyl)amino H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 129 H (2-amino-2-oxoethyl)amino H H H H3,5- (1S)-2,3-dihydro dichlorophenyl 1H-inden-1-yl 130 H dimethylamino HH H H 3-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 131 Hmethoxyamino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 132 H dimethylamino H H H H 2,3,5- (4S)-3,4-dihydro-trichlorophenyl 2H-chromen-4-yl 133 H morpholin-4-yl H H H H 2,3,5-(4S)-3,4-dihydro- trichlorophenyl 2H-chromen-4-yl 134 H methylamino H HH H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 135 Hazetidin-1-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 136 H pyridin-4-ylamino H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 137 H (2-ethoxy-2- H H H H 3,5-(4S)-3,4-dihydro- oxoethyl)(methyl)amino dichlorophenyl 2H-chromen-4-yl138 H (2- H H H H 3,5- (4S)-3,4-dihydro- hydroxyethyl)(methyl)aminodichlorophenyl 2H-chromen-4-yl 139 H dimethylamino H fluoro H H 3,4-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 140 H dimethylamino Hfluoro H H 3,4- (4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 141 Hdimethylamino H fluoro H H 3-chlorophenyl (4S)-3,4-dihydro-2H-chromen-4-yl 142 H morpholin-4-yl H fluoro H H 3,5- (4S)-3,4-dihydro-difluorophenyl 2H-chromen-4-yl 143 H morpholin-4-yl H fluoro H H3-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 144 Hmorpholin-4-yl H H fluoro H 3,4- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 145 H dimethylamino H H fluoro H 3,4- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 146 H dimethylamino H H fluoro H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 147 H dimethylamino H HH H 3,5- (4S)-6-methoxy- dichlorophenyl 3,4-dihydro-2H- chromen-4-yl 148H dimethylamino H H H H 3,5- (1S)-5-methoxy- dichlorophenyl2,3-dihydro-1H- inden-1-yl 149 H methyl[2-(morpholin-4- H H H H 3,5-(4S)-3,4-dihydro- yl)ethyl]amino dichlorophenyl 2H-chromen-4-yl 150 H(carboxymethyl)(methyl) H H H H 3,5- (4S)-3,4-dihydro- aminodichlorophenyl 2H-chromen-4-yl 151 H dimethylamino H H H H 3-(4S)-3,4-dihydro- (dimethylamino)- 2H-chromen-4-yl 2,4- difluorophenyl152 H dimethylamino H H H H 3,5- (4S)-7-fluoro-3,4- dichlorophenyldihydro-2H- chromen-4-yl 153 H ethylamino H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 154 H 2-acetylhydrazino H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 155 H morpholin-4-yl Hfluoro H H 3-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl156 H morpholin-4-yl H fluoro H H 3,4- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 157 H morpholin-4-yl H fluoro H H 3,4- (4S)-3,4-dihydro-difluorophenyl 2H-chromen-4-yl 158 H morpholin-4-yl H H fluoro H 3,4-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 159 H morpholin-4-yl HH fluoro H 3-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 160 Hmorpholin-4-yl H H fluoro H 3-chloro-2- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 161 H morpholin-4-yl H H fluoro H 2-chloro-3-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 162 H morpholin-4-yl H Hfluoro H 3,5- (4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 163 Hmorpholin-4-yl H H fluoro H 3-chloro-5- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 164 H morpholin-4-yl H H fluoro H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 165 H morpholin-4-yl H Hfluoro H 2-chloro-4- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 166H morpholin-4-yl H H fluoro H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 167 H morpholin-4-yl H fluoro H H 3-chlorophenyl(4S)-3,4-dihydro- 2H-chromen-4-yl 168 H dimethylamino H fluoro H H 3,5-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 169 H dimethylamino Hfluoro H H 3-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl170 H morpholin-4-yl H fluoro H H 5-chloro-2- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 171 H dimethylamino H fluoro H H3-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 172 Hdimethylamino H fluoro H H 2-chloro-4- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 173 H dimethylamino H H fluoro H 3,4- (4S)-3,4-dihydro-difluorophenyl 2H-chromen-4-yl 174 H dimethylamino H H fluoro H3-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 175 H dimethylamino H Hfluoro H 3-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 176H dimethylamino H H fluoro H 2-chloro-3- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 177 H dimethylamino H H fluoro H 3,5- (4S)-3,4-dihydro-difluorophenyl 2H-chromen-4-yl 178 H dimethylamino H H fluoro H3-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 179 Hdimethylamino H H fluoro H 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 180 H dimethylamino H H fluoro H 2-chloro-4-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 181 H thiomorpholin-4-ylH H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 182 H(2-tert-butoxy-2- H H H H 3,5- (4S)-3,4-dihydro- oxoethyl)aminodichlorophenyl 2H-chromen-4-yl 183 H (2-tert-butoxy-2- H H H H 3,5-(4S)-3,4-dihydro- oxoethyl)(methyl)amino dichlorophenyl 2H-chromen-4-yl184 H propylamino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 185 H (2-aminoethyl)amino H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 186 H (3R)-3-hydroxypyrrolidin-1-yl H H HH 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 187 H(3S)-3-hydroxypyrrolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 188 H 1H-1,2,3-triazol-1-yl H H H H 3,5-(4S)-3,4-dihydro dichlorophenyl 2H-chromen-4-yl 189 H2H-1,2,3-triazol-2-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 190 H morpholin-4-yl H H H H 3-chloro-4-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 191 H morpholin-4-yl H HH H 5-chloro-2,4- (4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 192 Hmorpholin-4-yl H fluoro H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 193 H (3rac)-3-hydroxypyrrolidin-1- H H H H3,5-dichloro-4- (4S)-3,4-dihydro- yl fluorophenyl 2H-chromen-4-yl 194 H(3rac)-3-hydroxypyrrolidin-1- H H H H 2,3- (4S)-3,4-dihydro- yldichlorophenyl 2H-chromen-4-yl 195 H (3rac)-3-hydroxypyrrolidin-1- H H HH 5-chloro-2,4- (4S)-3,4-dihydro- yl difluorophenyl 2H-chromen-4-yl 196H (3rac)-3-hydroxypyrrolidin-1- H H H H 3-chloro-4- (4S)-3,4-dihydro- ylfluorophenyl 2H-chromen-4-yl 197 H dimethylamino H H H H 5-chloro-2,4-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 198 meth- dimethylaminoH H H H 3,5- (4S)-3,4-dihydro- yl dichlorophenyl 2H-chromen-4-yl 199 Hmethyl(phenyl)amino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 200 H morpholin-4-yl H fluoro H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 201 H 3,3-difluoropyrrolidin-1-yl H H H H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 202 H3-oxopyrazolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 203 H 1,1-dioxidothiomorpholin-4-yl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 204 H morpholin-4-yl HH H H 2,3-dihydro-1- (4S)-3,4-dihydro- benzofuran-7-yl 2H-chromen-4-yl205 H morpholin-4-yl H chloro H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 206 H morpholin-4-yl H chloro H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 207 H dimethylamino H chloro H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 208 H dimethylamino Hchloro H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 209 Hmorpholin-4-yl H H H fluoro 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 210 H morpholin-4-yl H H H fluoro 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 211 H morpholin-4-yl H H chloro H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 212 H morpholin-4-yl HH chloro H 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 213 Hdimethylamino H H chloro H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 214 H morpholin-4-yl H H H methyl 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 215 H morpholin-4-yl H H H methyl 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 216 H morpholin-4-yl HH H H 5- (4S)-3,4-dihydro- (methoxycarbo- 2H-chromen-4-yl nyl)-1,3-benzoxazol-7-yl 217 H dimethylamino H H H methyl 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 218 H dimethylamino H H H methyl 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 219 H dimethylamino H HH H 2,4-difluoro-3- (4S)-3,4-dihydro- hydroxyphenyl 2H-chromen-4-yl 220H morpholin-4-yl H H H H 3-fluoro-2- (4S)-3,4-dihydro- methylphenyl2H-chromen-4-yl 221 H morpholin-4-yl H H H H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 222 H morpholin-4-yl H HH H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 223 H(3rac)-3-hydroxypyrrolidin-1- H H H H 5-chloro-2- (4S)-3,4-dihydro- ylfluorophenyl 2H-chromen-4-yl 224 H morpholin-4-yl H H H H 1,3-(4S)-3,4-dihydro- benzothiazol-4- 2H-chromen-4-yl yl 225 Hmorpholin-4-yl H H H H 3-fluoro-5- (4S)-3,4-dihydro- methylphenyl2H-chromen-4-yl 226 H morpholin-4-yl H H H H 3-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 227 H morpholin-4-yl H HH H 2-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 228 Hmorpholin-4-yl H H H H 3-chloro-5- (4S)-3,4-dihydro- methoxyphenyl2H-chromen-4-yl 229 H methylamino H H H H 3-chlorophenyl(4S)-3,4-dihydro- 2H-chromen-4-yl 230 H morpholin-4-yl H H H H2,5-difluoro-4- (4S)-3,4-dihydro- methoxyphenyl 2H-chromen-4-yl 231 Hmorpholin-4-yl H H H H 5-chloro-2- (4S)-3,4-dihydro- fluoro-4-2H-chromen-4-yl methylphenyl 232 H morpholin-4-yl H H H H3,4-difluoro-2- (4S)-3,4-dihydro- methoxyphenyl 2H-chromen-4-yl 233 Hmorpholin-4-yl H trifluoromethyl H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 234 H morpholin-4-yl H H H H 3,5-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 235 H morpholin-4-yl HH H H 3-chloro-5- (4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-ylphenyl 236 H methylamino H H H H 3-chloro-2- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 237 H methylamino H H H H 2,3,5-(4S)-3,4-dihydro- trichlorophenyl 2H-chromen-4-yl 238 H morpholin-4-yl HH H H 2-chloro-3- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 239 Hmorpholin-4-yl H H H H 5-chloro-2- (4S)-3,4-dihydro- fluoro-3-2H-chromen-4-yl methylphenyl 240 H morpholin-4-yl H H H H 3-chloro-2-(4S)-3,4-dihydro- fluoro-5- 2H-chromen-4-yl methylphenyl 241 H(2S)-2-(tert- H H H H 3,5- (1S)-2,3-dihydro-butoxycarbonyl)pyrrolidin-1- dichlorophenyl 1H-inden-1-yl yl 242 H(2S)-2-(tert- H H H H 3,5- (4S)-3,4-dihydro-butoxycarbonyl)pyrrolidin-1- dichlorophenyl 2H-chromen-4-yl yl 243 H(2R)-2-(tert- H H H H 3,5- (4S)-3,4-dihydro-butoxycarbonyl)pyrrolidin-1- dichlorophenyl 2H-chromen-4-yl yl 244 H(3rac)-3-hydroxypyrrolidin-1- H H H H 3-fluoro-5- (4S)-3,4-dihydro- ylmethylphenyl 2H-chromen-4-yl 245 H (3rrac)-3-hydroxypyrrolidin-1- H H HH 3,4-difluoro-2- (4S)-3,4-dihydro- yl methoxyphenyl 2H-chromen-4-yl 246H (3rac)-3-hydroxypyrrolidin-1- H H H H 2,5-difluoro-4-(4S)-3,4-dihydro- yl methoxyphenyl 2H-chromen-4-yl 247 H dimethylamino HH H H 2,3,6- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 248 Hmethoxy(methyl)amino H H H H 2-chlorophenyl (4S)-3,4-dihydro-2H-chromen-4-yl 249 H methoxy(methyl)amino H H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 250 Hmethoxy(methyl)amino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 251 H morpholin-4-yl H H H H 1,3- (4S)-3,4-dihydro-benzothiazol-7- 2H-chromen-4-yl yl 252 H cyclopropyl(methyl)amino H H HH 2-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 253 Hcyclopropyl(methyl)amino H H H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 254 H cyclopropyl(methyl)amino H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 255 H (2S)-2- H H H H3,5- (4S)-3,4-dihydro- (methoxycarbonyl)pyrrolidin- dichlorophenyl2H-chromen-4-yl 1-yl 256 H dimethylamino H trifluoromethyl H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 257 H(3rac)-3-hydroxypyrrolidin-1- H H H H 3,5- (4S)-3,4-dihydro- yldifluorophenyl 2H-chromen-4-yl 258 H (3rac)-3-hydroxypyrrolidin-1- H H HH 2-chloro-3- (4S)-3,4-dihydro- yl fluorophenyl 2H-chromen-4-yl 259 H(3rac)-3-hydroxypyrrolidin-1- H H H H 2-chloro-5- (4S)-3,4-dihydro- ylfluorophenyl 2H-chromen-4-yl 260 H (3rac)-3-hydroxypyrrolidin-1- H H H H3-chlorophenyl (4S)-3,4-dihydro- yl 2H-chromen-4-yl 261 H(3rac)-3-hydroxypyrrolidin-1- H H H H 3-chloro-5- (4S)-3,4-dihydro- ylmethoxyphenyl 2H-chromen-4-yl 262 H (3rac)-3-hydroxypyrrolidin-1- H H HH 3-chloro-2- (4S)-3,4-dihydro- yl fluorophenyl 2H-chromen-4-yl 263 H(2R)-2- H H H H 3,5- (4S)-3,4-dihydro- (methoxycarbonyl)pyrrolidin-dichlorophenyl 2H-chromen-4-yl 1-yl 264 H 2,2-dimethylpyrrolidin-1-yl HH H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 265 Hethylamino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl266 H (2S)-2-carboxypyrrolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 267 H morpholin-4-yl H H H H 5-chloro-2-(4S)-3,4-dihydro- methoxyphenyl 2H-chromen-4-yl 268 H morpholin-4-yl H HH H 5-fluoro-2- (4S)-3,4-dihydro- methoxyphenyl 2H-chromen-4-yl 269 H(3rac)-3-hydroxypyrrolidin-1- H H H H 5-chloro-2- (4S)-3,4-dihydro- ylmethoxyphenyl 2H-chromen-4-yl 270 H (3rac)-3-hydroxypyrrolidin-1- H H HH 5-fluoro-2- (4S)-3,4-dihydro- yl methoxyphenyl 2H-chromen-4-yl 271 H(3rac)-3-hydroxypyrrolidin-1 H H H H 3-chloro-5- (4S)-3,4-dihydro- yl(trifluoromethyl) 2H-chromen-4-yl phenyl 272 H(3rac)-3-hydroxypyrrolidin-1- H H H H 5-chloro-2- (4S)-3,4-dihydro- ylfluoro-3- 2H-chromen-4-yl methylphenyl 273 H cyclopropylamino H H H H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 274 H(2R)-2-carboxypyrrolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 275 H (3rac)-3-hydroxypyrrolidin-1- H H HH 3-chloro-2- (4S)-3,4-dihydro- yl fluoro-5- 2H-chromn-4-yl methylphenyl276 H (carboxylatomethyl)amino H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 277 H dimethylamino H H H H 2,6-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 278 H morpholin-4-yl Hfluoro H H 2,6- (4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 279 Hdimethylamino H fluoro H H 2,6- (4S)-3,4-dihydro- difluorophenyl2H-chromen-4-yl 280 H morpholin-4-yl H H H H 1,3-benzoxazol-(4S)-3,4-dihydro- 7-yl 2H-chromen-4-yl 281 H (3S)-3- H H H H 3,5-(4S)-3,4-dihydro- (methoxycarbonyl)pyrrolidin- dichlorophenyl2H-chromen-4-yl 1-yl 282 H (3R)-3- H H H H 3,5- (4S)-3,4-dihydro-(methoxycarbonyl)pyrrolidin- dichlorophenyl 2H-chromen-4-yl 1-yl 283 H(3R)-3-hydroxypyrrolidin-1-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 284 H (3S)-3-hydroxypyrrolidin-1-yl H H HH 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 285 H[(diethyoxyphosphoryl)methyl] H H H H 3,5- (4S)-3,4-dihydro-(methyl)amino dichlorophenyl 2H-chromen-4-yl 286 H[2-(cyclopropylamino)ethyl] H H H H 3,5- (4S)-3,4-dihydro- aminodichlorophenyl 2H-chromen-4-yl 287 H (2R)-2- H H H H 3,5-(4S)-3,4-dihydro- (hydroxymethyl)pyrrolidin-1- dichlorophenyl2H-chromen-4-yl yl 288 H (2S)-2- H H H H 3,5- (4S)-3,4-dihydro-(hydroxymethyl)pyrrolidin-1- dichlorophenyl 2H-chromen-4-yl yl 289 H[(1R,3)S-3-amino-2,2- H H H H 3,5- (4S)-3,4-dihydro-dimethylcyclopropyl]amino dichlorophenyl 2H-chromen-4-yl 290 H(2S)-2-methylmorpholin-4-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 291 H (3rac,4rac)-3-amino-4- H H H H 3,5-(4S)-3,4-dihydro- fluoropyrrolidin-1-yl dichlorophenyl 2H-chromen-4-yl292 H (2rac)-2-carboxypyrrolidin-1- H H H H 3,5- (1S)-2,3-dihydro- yldichlorophenyl 1H-inden-1-yl 293 H dimethylamino H H H H 3,4-dichloro-5-(4S)-3,4-dihydro- (dimethylamino) 2H-chromen-4-yl phenyl 294 Hdimethylamino H H H H 3-chloro-5- (4S)-3,4-dihdyro- (dimethylamino)2H-chromen-4-yl phenyl 295 H (3rac)-3-hydroxypyrrolidin-1- H H H H5-chloro-2- (4S)-3,4-dihydro- yl fluoro-4- 2H-chormen-4-yl methylphenyl296 H dimethylamino H H H H phenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 297H (2-hydroxyethyl)amino H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 298 H (2-methoxyethyl)amino H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 299 H (2R)-2-carboxylatopyrrolidin- H H H H3,5- (1S)-2,3-dihydro- 1-yl dichlorophenyl 1H-inden-1-yl 300 H 6-oxa-3-H H H H 3,5- (4S)-3,4-dihydro- azabicyclo[3.1.1]hept-3-yl dichlorophenyl2H-chromen-4-yl 301 H 3,9-dioxa-7- H H H H 3,5- (4S)-3,4-dihydro-azabicyclo[3.3.1]non-7-yl dichlorophenyl 2H-chromen-4-yl 302 H8-oxa-3-azabicyclo[3.2.1]oct- H H H H 3,5- (4S)-3,4-dihydro- 3-yldichlorophenyl 2H-chromen-4-yl 303 H (2R,6)S-2,6- H H H H 3,5-(4S)-3,4-dihydro- dimethylmorpholin-4-yl difluorophenyl 2H-chromen-4-yl304 H (2R,6S)-2,6- H H H H 2,3- (4S)-3,4-dihydro- dimethylmorpholin-4-yldichlorophenyl 2H-chromen-4-yl 305 H (2R,6S)-2,6- H H H H 2,3-(1S)-2,3-dihydro- dimethylmorpholin-4-yl dichlorophenyl 1H-inden-1-yl306 H (2R,6S)-2,6- H H H H 3,5- (1S)-2,3-dihydro- dimethylmorpholin-4-yldifluorophenyl 1H-inden-1-yl 307 H dimethylamino H H H H 4-chloro-3-(4S)-3,4-dihydro- (dimethylamino) 2H-chromen-4-yl phenyl 308 Hdimethylamino H H H H 3,5-dichloro-4- (4S)-3,4-dihydro- (dimethylamino)2H-chromen-4-yl phenyl 309 H morpholin-4-yl H methyloxy H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 310 H morpholin-4-yl Hmethyloxy H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 311H dimethylamino H H H H 3-chloro-4- (4S)-3,4-dihydro- (dimethylamino)2H-chromen-4-yl phenyl 312 H dimethylamino H H H H 3- (4S)-3,4-dihydro-(methylamino)phe- 2H-chrome-4-yl nyl 313 H morpholin-4-yl H H H H 2,6-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 314 H morpholin-4-yl Htrifluoromethyl H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 315 H dimethylamino H trifluoromethyl H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 316 H dimethylamino H Hchloro H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 317 H(3rac)-3-hydroxypyrrolidin-1- H H H H 3,5- (4S)-3,4-dihydro- yldichlorophenyl 2H-chromen-4-yl 318 H (3S)-3- H H H H 3,5-(4S)-3,4-dihydro- (hydroxymethyl)pyrrolidin-1- dichlorophenyl2H-chromen-4-yl yl 319 H morpholin-4-yl H H H H 2-chlorophenyl(4S)-3,4-dihydro- 2H-chromen-4-yl 320 H (2S)-2- H H H H 3,5-(4S)-3,4-dihydro- (ethoxycarbonyl)pyrrolidin-1- dichlorophenyl2H-chromen-4-yl yl 321 H 2,4-dimethyl-3,5-dioxo-1,2,4- H H H H 2,3-(4S)-3,4-dihydro- triazolidin-1-l dichlorophenyl 2H-chromen-4-yl 322 Hmorpholin-4-yl H H H H 3- (4S)-3,4-dihydro- (trifluoromethoxy)2H-chromen-4-yl phenyl 323 H dimethylamino H H H H 3-chloro-5-(4S)-3,4-dihydro- (morpholin-4- 2H-chromen-4-yl yl)phenyl 324 Hdimethylamino H H H H 2-chloro-4- (4S)-3,4-dihydro- (dimethylamino)2H-chromen-4-yl phenyl 325 H dimethylamino H H H H 3-chloro-4-(4S)-3,4-dihydro- (dimethylamino)- 2H-chromen-4-yl 5-fluorophenyl 326 Hdimethylamino H methyloxy H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 327 H dimethylamino H methyloxy H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 328 Hmethyl[2-(2-oxopyrrolidin-1- H H H H 3,5- (4S)-3,4-dihydro-yl)ethyl]amino dichlorophenyl 2H-chromen-4-yl 329 H (3R)-3- H H H H 3,5-(4S)-3,4-dihydro- (hydroxymethyl)pyrrolidin-1- dichlorophenyl2H-chromen-4-yl yl 330 H dimethylamino H fluoro H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 331 Hmethyl(oxetan-3-yl)amino H H H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 332 H (3R)-3-carboxypyrrolidin-1-yl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 333 H methyloxy H H H H3,5-dichloro-4- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 334 Hethyloxy H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 335H isopropyloxy H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 336 H isopropyloxy H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 337 H cylcopentyloxy H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 338 H (2-methoxyethyl)oxyH H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 339 Htetrahydro-2H-pyran-4-yloxy H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 340 H (2-hydroxyethyl)oxy H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 341 H ethyloxy H H H H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 342 H(3,3-dimethylbutyl)oxy H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 343 H (3-fluorobenzyl)oxy H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 344 H (2,3-difluorobenzyl)oixy H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 345 H(3-methoxybenzyl)oxy H H H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 346 H (3R)-pyrrolidin-3-yloxy H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 347 H (3-methoxy-3- H H HH 3,5- (1S)-2,3-dihydro- methylbutyl)oxy dichlorophenyl 1H-inden-1-yl348 H (cyclopentylmethyl)oxy H H H H 3,5- (1S)-2,3-dihydro-dichlorophenyl 1H-inden-1-yl 349 H isopropyloxy H H H H 3,5-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 350 H ethyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 351 H ethyl H H H H3-chloro-5- (4S)-3,4-dihydro- ethylphenyl 2H-chromen-4-yl 352 H methyl HH H H 3-chloro-5- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 353 Hmethyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 354H 1-cyano-2-ethoxy-2-oxoethyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 355 H cyanomethyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 356 H propyl H H H H3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 357 Hprop-1-en-2-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 358 H cyclopropyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 359 H isopropyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 360 H2-amino-2-oxoethyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 361 H nitrilomethyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 362 H (2-hydroxyethyl)sulfanyl H H H H3,5- (1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 363 Hpyridin-2-ylsulfanoyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 364 H (2-hydroxyethyl)sulfamoyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 365 H methylsulfanoyl HH H H 3-chloro-5- (4S)-3,4-dihydro- (methylsulfanyl) 2H-chromen-4-ylphenyl 366 H ethylsulfanoyl H H H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 367 H ethylsulfanoyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 368 H ethylsulfinyl H HH H 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 369 Hethylsulfonyl H H H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 370 H ethylsulfinyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 371 H ethylsulfonyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 372 H(2-carboxyethyl)sulfamoyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 373 H methyloxy H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 374 H (2rac)-2- H H H H 3,5-(4S)-3,4-dihydro- (trifluoromethyl)morpho- dichlorophenyl2H-chromen-4-yl lin-4-yl 375 H (2-methoxy-2- H H H H 3,5-(4S)-3,4-dihydro- oxoethyl)amino dichlorophenyl 2H-chromen-4-yl 376 H HH H H H 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 377 Hdimethylamino H H H H 5-fluoro-2- (4S)-3,4-dihydro- methoxypyridin-2H-chromen-4-yl 4-yl 378 H dimethylamino H H H H 2-cyanopyridin-(4S)-3,4-dihydro- 4-yl 2H-chromen-4-yl 379 H dimethylamino H H H H2-aminopyridin- (4S)-3,4-dihydro- 4-yl 2H-chromen-4-yl 380 Hdimethylamino H H H H 2- (4S)-3,4-dihydro- methylpyridin-2H-chromen-4-yl 4-yl 381 H dimethylamino H H H H 3- (4S)-3,4-dihydro-methylpyridin- 2H-chromen-4-yl 4-yl 382 H dimethylamino H H H H3-chloropyridin- (4S)-3,4-dihydro- 4-yl 2H-chromen-4-yl 383 Hdimethylamino H H H H 3-fluoropyridin- (4S)-3,4-dihydro- 4-yl2H-chromen-4-yl 384 H methylamino H H H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 385 H methylamino H H H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 386 H isopropyl H H HH 2,3,5- (4S)-3,4-dihydro- trichlorophenyl 2H-chromen-4-yl 387 Hdimethylamino H H H H 5-cyano-4- (4S)-3,4-dihydro- methyl-2-thienyl2H-chromen-4-yl 388 H dimethylamino H H H H 2,5-dimethyl-3-(4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 389 H dimethylamino H H H H5-cyano-2- (4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 390 H dimethyaminoH H H H 5-chloro-2- (4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 391 Hdimethylamino H H H H 5-methyl-2- (4S)-3,4-dihydro- thienyl2H-chromen-4-yl 392 H 3-fluoroazetidin-1-yl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 393 H4-fluoropiperidin-1-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 394 H 3,3-difluoroazetidin-1-yl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 395 H methylamino Hfluoro H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 396 Hpyridin-4-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 397 H 2-oxo-1,2- H H H H 3,5- (4S)-3,4-dihydro-dihydropyridin-5-yl dichlorophenyl 2H-chromen-4-yl 398 H4,4-difluoropiperidin-1- H H H H 3,5- (4S)-3,4-dihydro- yldichlorophenyl 2H-chromen-4-yl 399 H dimethylamino H H H H2-morpholin-4- (4S)-3,4-dihydro- ylpyridin-4-yl 2H-chromen-4-yl 400 Hdimethylamino H H H H 5-chloro-2- (4S)-3,4-dihydro- methoxypyridin-2H-chromen-4-yl 4-yl 401 H dimethylamino H H H H 3- (4S)-3,4-dihydro-methoxypyridin- 2H-chromen-4-yl 4-yl 402 H dimethylamino H H H H 2-(4S)-3,4-dihydro- (hydroxymethyl) 2H-chromen-4-yl pyridin-4-yl 403 Hdimethylamino H H H H 3,5- (4S)-3,4-dihydro- difluoropyridin-2H-chromen-4-yl 4-yl 404 H cyclobutyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 405 H 2-hydroxyethylamino H H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 406 H isopropyl H H H H3-chlorophenyl (4S)-3,4-dihydro- 2H-chromen-4-yl 407 H isopropyl H H H H3- (4S)-3,4-dihydro- (trifluoromethoxy) 2H-chromen-4-yl phenyl 408 Hisopropyl H H H H 2-fluoro-3- (4S)-3,4-dihydro- (trifluoromethyl)2H-chromen-4-yl phenyl 409 H isopropyl H H H H 3-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 410 H isopropyl H H H H5-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 411 Hisopropyl H H H H 3- (4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-ylphenyl 412 H 2-aminopyrimidin-5-yl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 413 H dimethylamino H H H H 2,6-(4S)-3,4-dihydro- difluoropyridin- 2H-chromen-4-yl 4-yl 414 Hdimethylamino H H H H 2-chloro-3- (4S)-3,4-dihydro- fluoropyridin-4-2H-chromen-4-yl yl 415 H dimethylamino H H H H 2,5- (4S)-3,4-dihydro-dichloropyridin- 2H-chromen-4-yl 4-yl 416 H dimethylamino H H H H5-fluoro-2- (4S)-3,4-dihydro- isopropyloxy- 2H-chromen-4-yl pyridin-4-yl417 H dimethylamino H H H H 2-ethoxy-5- (4S)-3,4-dihydro-fluoropyridin-4- 2H-chromen-4-yl yl 418 H isopropyl H H H H 2-chloro-5-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 419 H isopropyl H H H H3-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 420 Hisopropyl H H H H 2-chloro-3- (4S)-3,4-dihydro- (trifluoromethyl)2H-chromen-4-yl phenyl 421 H isopropyl H H H H 2-chloro-3-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 422 H isopropyl H H H H2,5-dimethyl-3- (4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 423 Hisopropyl H H H H 2,5-dichloro-3- (4S)-3,4-dihydro- thienyl2H-chromen-4-yl 424 H 2-aminoethyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 425 H isopropyl H fluoro H H2,5-dimethyl-3- (4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 426 Hisopropyl H fluoro H H 2,5-dichloro-3- (4S)-3,4-dihydro- thienyl2H-chromen-4-yl 427 H methoxy(methyl)amino H H H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 428 H dimethylamino HH cyano H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 429 Hdimethylamino H H hydroxy H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 430 H isopropyl H H H H 3,5- (4S)-3,4-dihydro-difluorophenyl 2H-chromen-4-yl 431 H isopropyl H H H H 3-chloro-5-(4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-yl phenyl 432 H(dimethylamino)methyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 433 H dimethylamino H H H H 2,5- (4S)-3,4-dihydro-bis(trifluorometh- 2H-chromen-4-yl yl)phenyl 434 H dimethylamino H H H H5-fluoro-2- (4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-yl phenyl435 H dimethylamino H H H H 2-chloro-5- (4S)-3,4-dihydro- cyanophenyl2H-chromen-4-yl 436 H dimethylamino H H H H 5-fluoro-2-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 437 H dimethylamino H H HH 2-fluoro-5- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 438 Hisopropyl H H H H 3,5-dichloro-4- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 439 H 3-fluoro-2-oxo-1,2- H H H H 3,5- (4S)-3,4-dihydro-dihydropyridin-5-yl dichlorophenyl 2H-chromen-4-yl 440 H amino H H H H2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 441 Hmorpholin-4-yl H H H H 2,5-dichloro-3- (4S)-3,4-dihydro- thienyl2H-chromen-4-yl 442 H morpholin-4-yl H H H H 3-chloro-2-(4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 443 H morpholin-4-yl H H H H5-chloro-2- (4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 444 H isopropyl HH H H 3-chloro-2- (4S)-3,4-dihydro- fluoro-5- 2H-chromen-4-ylmethylphenyl 445 H 1,2-oxazolidin-2-yl H H H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 446 H isopropyl H H H H 3-chloro-4-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 447 H isopropyl H H H H2,5- (4S)-3,4-dihydro- dimethylphenyl 2H-chromen-4-yl 448 H isopropyl HH H H 3-fluoro-5- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 449 Hisopropyl H H H H 3,4,5- (4S)-3,4-dihydro- trifluorophenyl2H-chromen-4-yl 450 H isopropyl H H H H 2,3,5- (4S)-3,4-dihydro-trifluorophenyl 2H-chromen-4-yl 451 H isopropyl H H H H 2-methyl-5-(4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-yl phenyl 452 Hmethoxy(methyl)amino H H H H 2,3,5- (1S)-2,3-dihydro- trifluorophenyl1H-inden-1-yl 453 H isopropyl H H H H 2,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 454 H 1H-pyrazol-4-yl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 455 H isopropyl Hfluoro H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 456 Hdimethylamino H H H H 2-methyl-1,3- (4S)-3,4-dihydro- thiazol-5-yl2H-chromen-4-yl 457 H dimethylamino H H H H 4-chloro-2-(4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 458 H dimethylamino H H H H 5-(4S)-3,4-dihydro- (trifluoromethyl)- 2H-chromen-4-yl 2-thienyl 459 Hdimethylamino H H H H 5-fluoro-2- (4S)-3,4-dihydro- thienyl2H-chromen-4-yl 460 H dimethylamino H H H H 3,5- (4S)-3,4-dihydro-dichloropyridin- 2H-chromen-4-yl 4-yl 461 H morpholin-4-yl H H H H 2,5-(4S)-3,4-dihydro- bis(trifluorometh- 2H-chromen-4-yl yl)phenyl 462 Hmorpholin-4-yl H H H H 2,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 463 H morpholin-4-yl H H H H 5-fluoro-2-(4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-yl phenyl 464 Hmorpholin-4-yl H H H H 2-chloro-5- (4S)-3,4-dihydro- cyanophenyl2H-chromen-4-yl 465 H morpholin-4-yl H H H H 2-chloro-5-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 466 H morpholin-4-yl H HH H 5-fluoro-2- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 467 Hmorpholin-4-yl H H H H 2-fluoro-5- (4S)-3,4-dihydro- methylphenyl2H-chromen-4-yl 468 H moprholin-4-yl H H H H 2,5- (4S)-3,4-dihydro-dimethylphenyl 2H-chromen-4-yl 469 H dimethylamino H H H H 2,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 470 H dimethylamino H HH H 2-chloro-5- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 471 Hdimethylamino H H H H 2,5- (4S)-3,4-dihydro- dimethylphenyl2H-chromen-4-yl 472 H dimethylamino H H H H 2,6- (4S)-3,4-dihydro-dimethoxypyridin- 2H-chromen-4-yl 4-yl 473 H dimethylamino H H H H2-chloro-6- (4S)-3,4-dihydro- methylpyridin- 2H-chromen-4-yl 4-yl 474 Hdimethylamino H H H H 2,3- (4S)-3,4-dihydro- dimethoxypyridin-2H-chromen-4-yl 4-yl 475 H dimethylamino H H H H 3-chloro-2-(4S)-3,4-dihydro- methoxypyridin- 2H-chromen-4-yl 4-yl 476 Hdimethylamino H H H H 2,3- (4S)-3,4-dihydro- dichloropyridin-2H-chromen-4-yl 4-yl 477 H isopropyl H fluoro H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 478 H vinyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 479 H isopropyl Hfluoro H H 3- (4S)-3,4-dihydro- (trifluoromethoxy) 2H-chromen-4-ylphenyl 480 H morpholin-4-yl H H H H 2,5-dimethyl-3- (4S)-3,4-dihydro-thienyl 2H-chromen-4-yl 481 H morpholin-4-yl methyl H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 482 H 2,2- H H H H 2,3-(4S)-3,4-dihydro- difluoroethyl(methyl(ami- dichlorophenyl2H-chromen-4-yl no 483 H morpholin-4-yl methyl H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 484 H oxetan-3- H H H H2,3- (4S)-3,4-dihydro- ylmethylamino dichloropehnyl 2H-chromen-4-yl 485H morpholin-4-yl H fluoro H H 3,5- (1S)-2,3-dihydro- dichlorophenyl1H-inden-1-yl 486 H morpholin-4-yl H fluoro H H 1,3- (4S)-3,4-dihydro-benzothiazol-7- 2H-chromen-4-yl yl 487 H isopropyl H fluoro H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 488 H isopropyl Hfluoro H H 3- (4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-yl phenyl489 H 3-thienyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 490 H morpholin-4-yl H fluoro H H 2,5- (4S)-3,4-dihydro-dimethylphenyl 2H-chromen-4-yl 491 H morpholin-4-yl H fluoro H H 2,3-(1S)-2,3-dihydro- dichlorophenyl 1H-inden-1-yl 492 H morpholin-4-yl Hfluoro H H 2,3- (1S)-1,2,3,4- dichlorophenyl tetrahydronaphth- alen-1-yl493 H dimethylamino H H H H 3,5- (3rac)-2,3- dichlorophenyl dihydro-1-benzothiophen-3- yl 494 H cyclopentyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 495 H moprholin-4-yl H H H H2,3-dichloro-5- (4S)-3,4-dihydro- hydroxyphenyl 2H-chromen-4-yl 496 Hmorpholin-4-yl H H H methoxy 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 497 H morpholin-4-yl H H H methoxy 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 498 H morpholin-4-yl H Hmethoxy H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 499 Hmorpholin-4-yl H H methoxy H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 500 H moprholin-4-yl H H methoxy H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 501 H dimethylamino H Hmethoxy H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 502 Hdimethylamino H H methoxy H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 503 H dimethylamino H H methoxy H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 504 H dimethylamino H H Hmethoxy 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 505 Hdimethylamino H H H methoxy 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 506 H dimethylamino H H H methoxy 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 507 H dimethylamino H H Hchloro 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 508 Hdimethylamino H H H chloro 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 509 H dimethylamino H H H chloro 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 510 H dimethylamino H Htrifluoro- H 2,3- (4S)-3,4-dihydro- methyl dichlorophenyl2H-chromen-4-yl 511 H dimethylamino H H trifluoro- H 5-chloro-2-(4S)-3,4-dihydro- methyl fluorophenyl 2H-chromen-4-yl 512 Hmorpholin-4-yl H H trifluoro- H 3,5- (4S)-3,4-dihydro- methyldichlorophenyl 2H-chromen-4-yl 513 H morpholin-4-yl H H trifluoro- H2,3- (4S)-3,4-dihydro- methyl dichlorophenyl 2H-chromen-4-yl 514 Hmorpholin-4-yl H H trifluoro- H 5-chloro-2- (4S)-3,4-dihydro- methylfluorophenyl 2H-chromen-4-yl 515 H methyl(oxan-4- H H H H 2,3-(4S)-3,4-dihydro- ylmethyl)amino dichlorophenyl 2H-chromen-4-yl 516 Hmethoxy(methyl)amino H fluoro H H 2,3,5- (4S)-3,4-dihydro-trifluorophenyl 2H-chromen-4-yl 517 H morpholin-4-yl H H hydroxy H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 518 H oxetan-3- H H H H3,5- (4S)-3,4-dihydro- ylmethylamino dichlorophenyl 2H-chromen-4-yl 519H (3rac)-pyrrolidin-3-yl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 520 H 1-(difluoromethyl)-1H- H H H H 3,5-(4S)-3,4-dihydro- pyrazol-4-yl dichlorophenyl 2H-chromen-4-yl 521 Hmorpholin-4-yl H H hydroxy H 2,3-dichloro-5- (4S)-3,4-dihydro-hydroxyphenyl 2H-chromen-4-yl 522 H dimethylamino methyl H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 523 H dimethylaminomethyl H H H 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 524 Hdimethylamino methyl H H H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl2H-chromen-4-yl 525 H ethyl(methyl)amino H H H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 526 H isopropyl(methyl)amino H H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 527 Hethyl(methyl)amino H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 528 H dimethylamino H amino H H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 529 H dimethylamino Hamino H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 530 Hmorpholin-4-yl H H H methoxy 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 531 H morpholin-4-yl H H H chloro 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 532 H morpholin-4-yl H HH chloro 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 533 Hmorpholin-4-yl H H H chloro 3,5- (4S)-3,5-dihydro- dichlorophenyl2H-chromen-4-yl 534 H isopropyl(methyl)amino H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 535 Hmethoxy(methyl)amino H chloro H H 2,6- (4S)-3,4-dihydro-dichloropyridin- 2H-chromen-4-yl 4-yl 536 H morpholin-4-yl H amino H H5-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 537 Hmorpholin-4-yl H amino H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 538 H morpholin-4-yl H amino H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 539 H oxan-4-yl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 540 H morpholin-4-yl Hfluoro H H 3,4,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 541H methylamino H fluoro H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 542 H methylamino H fluoro H H 2,3,5- (4S)-3,4-dihydro-trifluorophenyl 2H-chromen-4-yl 543 H morpholin-4-yl H fluoro H H2,5-dichloro-3- (4S)-3,4-dihydro- thienyl 2H-chromen-4-yl 544 Hmorpholin-4-yl H fluoro H H 2,5-dimethyl-3- (4S)-3,4-dihydro- thienyl2H-chromen-4-yl 545 H methylamino H fluoro H H 2,6- (4S)-3,4-dihydro-dichloropyridin- 2H-chromen-4-yl 4-yl 546 H morpholin-4-yl H fluoro H H4- (4S)-3,4-dihydro- (difluoromethoxy)- 2H-chromen-4-yl yl)-3,5-difluorophenyl 547 H methylamino H fluoro H H 4- (4S)-3,4-dihydro-(difluoromethoxy)- 2H-chromen-4-yl 3,5- difluorophenyl 548 Hmoprholin-4-yl H fluoro H H 2,3- (4S)-3,4-dihydro- difluorophenyl2H-chromen-4-yl 549 H morpholin-4-yl H fluoro H H 2,3,4-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 550 H morpholin-4-yl Hfluoro H H 2,6- (4S)-3,4-dihydro- dichloropyridin- 2H-chromen-4-yl 4-yl551 H dimethylamino H amino H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 552 H methyl H H H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 553 H morpholin-4-yl H chloro H H 2,6-(4S)-3,4-dihydro- dichloropyridin- 2H-chromen-4-yl 4-yl 554 H methyl H HH H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chroman-4-yl 555 Hdimethylamino H H H H 3,5- (1rac)-1-methyl- dichlorophenyl3,4-dihydro-2H- naphthalen-1-yl 556 H morpholin-4-yl H chloro H H 3,5-(4S)-3,4-dihydro- difluorophenyl 2H-chromen-4-yl 557 H morpholin-4-yl Hchloro H H 3-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl558 H morpholin-4-yl H chloro H H 3- (4S)-3,4-dihydro- (trifluoromethyl)2H-chromen-4-yl phenyl 559 H dimethylamino H hydroxy H H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 560 H dimethylamino Hhydroxy H H 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 561 Hdimethylamino H hydroxy H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 562 H 4-oxoimidazolidin-1-yl H H H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 563 H4-oxoimidazolidin-1-yl H H H H 2,3,5- (4S)-3,4-dihydro- trichlorophenyl2H-chromen-4-yl 564 H morpholin-4-yl H chloro H H 3-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 565 H morpholin-4-yl Hchloro H H 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl566 H 2-hydroxyethylamino H H H H 2,3,5- (4S)-3,4-dihydro-trichlorophenyl 2H-chromen-4-yl 567 H 2-hydroxyethylamnio H H H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 568 H2-hydroxyethylamino H H H H 2,6- (4S)-3,4-dihydro- dichloropyridin-2H-chromen-4-yl 4-yl 569 H 4-oxoimidazolidin-1-yl H H H H 3-(4S)-3,4-dihydro- (trifluoromethoxy) 2H-chromen-4-yl phenyl 570 H ethylH H H H 3- (4S)-3,4-dihydro- (trifluoromethoxy) 2H-chromen-4-ylyl)phenyl 571 H methyl H H H H 3- (4S)-3,4-dihydro- (trifluoromethoxy)2H-chromen-4-yl phenyl 572 H methyl H H H H 2,3,5- (4S)-3,4-dihydro-trichlorophenyl 2H-chromen-4-yl 573 H ethyl H H H H 2,3,5-(4S)-3,4-dihydro- trichlorophenyl 2H-chromen-4-yl 574 H dimethylamino HH H H 3,5- (4S)-3,4-dihydro- diethylphenyl 2H-chromen-4-yl 575 H ethyl HH H H 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 576 Hmorpholin-4-yl H chloro H H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl2H-chromen-4-yl 577 H 2-hydroxyethylamino H fluoro H H 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 578 H2-hydroxyethylamino H fluoro H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 579 H 2-hydroxyethylamino H fluoro H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 580 H dimethylamino HH H H 3,5- (4rac)-6- dichlorophenyl bromochroman-4- yl 581 Hdimethylamino H H H H 3,5- (4rac)-3,4- dichlorophenyl dihydro-1H-isochromen-4-yl 582 H dimethylamino H H H H 2-chloro-3,5-(4S)-3,4-dihydro- diethylphenyl 2H-chromen-4-yl 583 H morpholin-4-yl H HH H 2-chloro-3,5- (4S)-3,4-dihydro- diethylphenyl 2H-chromen-4-yl 584 Hmorpholin-4-yl H hydroxy H H 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 585 H dimethylaminocarbonyl H H H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 586 H dimethylamino H HH H 3-tert-butyl-5- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 587 Hmoprholin-4-yl H H H H 3-tert-butyl-5- (4S)-3,4-dihydro- methylphenyl2H-chromen-4-yl 588 H morpholin-4-yl H H H H 3,5- (4S)-3,4-dihydro-diethylphenyl 2H-chromen-4-yl 589 H 2- H H H H 2,3- (4S)-3,4-dihydro-hydroxyethyl(methyl)a- dichlorophenyl 2H-chromen-4-yl mino 590 H 2- H HH H 2,3,5- (4S)-3,4-dihydro- hydroxyethyl(methyl)a- trichlorophenyl2H-chromen-4-yl mino 591 H 2- H H H H 2,6- (4S)-3,4-dihydro-hydroxyethyl(methyl)a- dichloropyridin- 2H-chromen-4-yl mino 4-yl 592 Hhydroxymethyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 593 H 2-hydroxyethyl H H H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 594 H morpholin-4-yl H H H H 3-cyano-5-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 595 H methyl-[[-(3rac)- Hfluoro H H 2,3- (4S)-3,4-dihydro- oxolan-3- dichlorophenyl2H-chromen-4-yl yl]methyl]amino 596 H 2-(1H-pyrazol-1- H fluoro H H2,3,5- (4S)-3,4-dihydro- yl)ethylamino trifluorophenyl 2H-chromen-4-yl597 H 2-hydroxyethylamino H fluoro H H 2,6- (4S)-3,4-dihydro-dichloropyridin- 2H-chromen-4-yl 4-yl 598 H dimethylamino H H H H3-cyano-5- (4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 599 H2-(1H-imidazol-1- H fluoro H H 2,3- (4S)-3,4-dihydro- yl)ethylaminodichlorophenyl 2H-chromen-4-yl 600 H methyl H H H H 2-chloro-5-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 601 H dimethylamino H H HH 5-tert-butyl-2- (4S)-3,4-dihydro- chloro-3- 2H-chromen-4-ylmethylphenyl 602 H 4-oxoimidazolidin-1-yl H H H H 2-chloro-5-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 603 H ethyl H H H H2-chloro-5- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 604 H4-oxoimidazolidin-1-yl H H H H 5-chloro-2- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 605 H methyl H H H H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 606 H 2- H H H H 2,3,5-(4S)-3,4-dihydro- hydroxyethyl(methyl)a- trifluorophenyl 2H-chromen-4-ylmino 607 H morpholin-4-yl H H H H 5-tert-butyl-2- (4S)-3,4-dihydro-chloro-3- 2H-chromen-4-yl methylphenyl 608 H morpholin-4-yl H H H H2,3-dichloro-5- (4S)-3,4-dihydro- cyanophenyl 2H-chromen-4-yl 609 Hmorpholin-4-yl H trifluoro- H H 5-chloro-2- (4S)-3,4-dihydro- methoxyfluorophenyl 2H-chromen-4-yl 610 H morpholin-4-yl H trifluoro- H H 2,3-(4S)-3,4-dihydro- methoxy dichlorophenyl 2H-chromen-4-yl 611 Hmorpholin-4-yl H trifluroo- H H 3,5- (4S)-3,4-dihydro- methoxydichlorophenyl 2H-chromen-4-yl 612 H dimethylamino H trifluoro- H H5-chloro-2- (4S)-3,4-dihydro- methoxy fluorophenyl 2H-chromen-4-yl 613 Hdimethylamino H trifluoro- H H 2,3- (4S)-3,4-dihydro- methoxydichlorophenyl 2H-chromen-4-yl 614 H dimethylamino H trifluoro- H H 3,5-(4S)-3,4-dihydro- methoxy dichlorophenyl 2H-chromen-4-yl 615 Hmorpholin-4-yl H hydroxy H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 616 H morpholin-4-yl H hydroxy H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 617 H dimethylamino Hcyano H H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 618 Hdimethylamino H H hydroxy H 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 619 H dimethylamino H H hydroxy H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 620 H dimethylamino H H H H 3,5-(4rac)-8- dichlorophenyl fluorochroman-4- yl 621 H dimethylamino H H H H3,5- (4rac)-6,8- dichlorophenyl dichlorochroman- 4-yl 622 Hdimethylamino H H H H 3,5- (4rac)-6- dichlorophenyl chlorochroman-4- yl623 H dimethylamino H H H H 3,5- (4rac)-6- dichlorophenylfluorochroman-4- yl 624 H dimethylamino H H H H 2,3-dichloro-5-(4S)-3,4-dihydro- cyanophenyl 2H-chromen-4-yl 625 H 2-(1H-imidazol-1- HH H H 3,5- (4S)-3,4-dihydro- yl)ethylamino dichlorophenyl2H-chromen-4-yl 626 H morpholin-4-yl H H hydroxy H 5-chloro-2-(4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 627 H morpholin-4-yl H Hhydroxy H 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 628 Hethyl H H H H 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl629 H methylamino H chloro H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 630 H morpholin-4-yl H chloro H H 3,5- (1rac)-3,3-dichlorophenyl dimethylindan-1- yl 631 H [acetyl(methyl)amino]meth- H HH H 3,5- (4S)-3,4-dihydro- yl dichlorophenyl 2H-chromen-4-yl 632 Hdimethylamino H H H H 3,5- (4rac)-8- dichlorophenyl chlorochroman-4- yl633 H dimethylamino H H H H 3,5- (4rac)-6,8- dichlorophenyldifluorochroman- 4-yl 634 H dimethylamino H H H H 3,5- (4rac)-8-dichlorophenyl bromochroman-4- yl 635 H morpholin-4-yl H chloro H H 3,5-(1rac)-3- dichlorophenyl oxoindan-1-yl 636 H methylamino H chloro H H2,3,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 637 Hethylamino H fluoro H H 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 638 H ethylamino H fluoro H H 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 639 H ethylamino H fluoro H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 640 H ethylamino Hfluoro H H 2,6- (4S)-3,4-dihydro- dichloropyridin- 2H-chromen-4-yl 4-yl641 H 2-acetyloxyethylamino H H H H 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 642 H morpholin-4-yl H cyano H H5-chloro-2- (4S)-3,4-dihydro- fluorophenyl 2H-chromen-4-yl 643 H2-(dimethylamino)ethyl H H H H 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 644 H 2-(1H-imidazol-1- H fluoro H H 3,5-(4S)-3,4-dihydro- yl)ethyl-methylamio dichlorophenyl 2H-chromen-4-yl 645H methyl H H H H 2-chloro-5- (4S)-3,4-dihydro- methylphenyl2H-chromen-4-yl 646 H ethyl H H H H 2-chloro-5- (4S)-3,4-dihydro-methylphenyl 2H-chromen-4-yl 647 H methyl(2- H fluoro H H 3,5-(4S)-3,4-dihydro- methylsulfonylethyl)ami- dichlorophenyl2H-chromen-4-yl no 648 H 3-fluoroazetidin-1-yl H fluoro H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 649 H 2- H fluoro H H3,5- (4S)-3,4-dihydro- hydroxyethyl(methyl)a- dihclorophenyl2H-chromen-4-yl mino 650 H (3-methoxy-3- H fluoro H H 3,5-(4S)-3,4-dihydro- oxopropyl)- dichlorophenyl 2H-chromen-4-yl methylamino651 H morpholin-4-yl H H H cyano 5-chloro-2- (4S)-3,4-dihydro-fluorophenyl 2H-chromen-4-yl 652 H morpholin-4-yl H cyano H H 3,5-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 653 H3,6-dihydro-2H-pyran- H H H H 2,3- (4S)-3,4-dihydro- 4-yl dichlorophenyl2H-chromen-4-yl 654 H 1,3-dimethyl-2,4-dioxo- H H H H 3,5-(4S)-3,4-dihydro- 1,2,3,4- dichlorophenyl 2H-chromen-4-yltetrahydropyrimidin-5-yl 655 H ethyl H H H H 2,3,5- (4S)-3,4-dihydro-trifluorophenyl 2H-chromen-4-yl 656 H dimethylamino H H H H 5-chloro-1H-(4S)-3,4-dihydro- imidazol-2-yl 2H-chromen-4-yl 657 H morpholin-4-yl H HH cyano 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 658 Hdimethylamino H H H cyano 5-chloro-2- (4S)-3,4-dihydro- fluorophenyl2H-chromen-4-yl 659 H dimethylamino H H H cyano 2,3- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 660 H oxetan-3-yl H H H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 661 H methyl(2- Hfluoro H H 2,6- (4S)-3,4-dihydro- methylsulfonylethyl)ami-dichloropyridin- 2H-chromen-4-yl no 4-yl 662 H iodo H H H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 663 H morpholin-4-yl HH H cyano 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 664 Hdimethylamino H H H cyano 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 665 H dimethylamino H H H H 3,5- (4rac)-8-fluoro-dichlorophenyl 3,4-dihydro-1H- isochromen-4-yl 666 H 2- H fluoro H H3,5- (1S)-2,3-dihydro- hydroxyethyl)methyl)a- dichlorophenyl1H-inden-1-yl mino 667 H dimethylamino H H H H 3,5- (1rac)-3-dichlorophenyl oxoindan-1-yl 668 H dimethylamino H chloro H H 2,6-(4S)-3,4-dihydro- dichloropyridin- 2H-chromen-4-yl 4-yl 669 Hdimethylamino H chloro H H 3,5- (4S)-3,4-dihydro- difluorophenyl2H-chromen-4-yl 670 H dimethylamino H chloro H H 3-tert-butyl-5-(4S)-3,4-dihydro- methylphenyl 2H-chromen-4-yl 671 H dimethylamino Hchloro H H 3- (4S)-3,4-dihydro- (trifluoromethyl) 2H-chromen-4-yl phenyl672 H dimethylamino H chloro H H 3,5- (4S)-3,4-dihydro- dimethylphenyl2H-chromen-4-yl 673 H 2-(1H-pyrazol-1- H fluoro H H 2,6-(4S)-3,4-dihydro- yl)ethylamino dichloropyridin- 2H-chromen-4-yl 4-yl674 H 2- H chloro H H 3,5- (4S)-3,4-dihydro- hydroxyethyl(methyl)a-dichlorophenyl 2H-chromen-4-yl mino 676 H ethyl H H H H 2,5-(4S)-3,4-dihydro- dimethylphenyl 2H-chromen-4-yl 677 H(3rac)-pyrrolidin-3-yl H H H H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl2H-chromen-4-yl 678 H (3rac)-tetrahydrofuran- H H H H 2,3,5-(4S)-3,4-dihydro- 3-yl trifluorophenyl 2H-chromen-4-yl 679 H1-methyl-piperidin-4-yl H H H H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl2H-chromen-4-yl 680 H morpholin-4-yl H H H hydroxy 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 681 H morpholin-4-yl HH H hydroxy 3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 682 Hdimethylamino H H H hydroxy 2,3- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 683 H dimethylamino H H H hydroxy 3,5- (4S)-3,4-dihydro-dichlorophenyl 2H-chromen-4-yl 684 H isopropyl H fluoro H H 2,5-(4S)-3,4-dihydro- dimethylphenyl 2H-chromen-4-yl 685 H methyl H H H H2,5- (4S)-3,4-dihydro- dimethylphenyl 2H-chromen-4-yl 686 Hmethoxymethyl H H H H 2,3,5- (4S)-3,4-dihydro- trifluorophenyl2H-chromen-4-yl 687 H ethyl H H H H 3,5- (4S)-3,4-dihydro-difluorophenyl 2H-chromen-4-yl 688 H ethyl H H H H 2,3,5-(4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl 689 H morpholin-4-yl Hfluoro H fluoro 2,3,5- (4S)-3,4-dihydro- trifluorophenyl 2H-chromen-4-yl690 H dimethylamino H fluoro H fluoro 2,3,5- (4S)-3,4-dihydro-trifluorophenyl 2H-chromen-4-yl 691 H morpholin-4-yl H fluoro H fluoro3,5- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 692 Hdimethylamino H fluoro H fluoro 3,5- (4S)-3,4-dihydro- dichlorophenyl2H-chromen-4-yl 693 H morpholin-4-yl H fluoro H fluoro 2,3-(4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl 694 H dimethylamino Hfluoro H fluoro 2,3- (4S)-3,4-dihydro- dichlorophenyl 2H-chromen-4-yl695 H methyl H H H H 3,5- (4S)-3,4-dihydro- difluorophenyl2H-chromen-4-yl

TABLE 2 LC-MS and NMR data NMR peak forms are stated as they appear inthe spectra, possible higher order effects have not been considered. NMRpeak lists ¹H-NMR data of selected examples are written in form of¹H-NMR peak lists. To each signal peak are listed the δ-value in ppm andthe signal intensity in round brackets. Between the δ-value - signalintensity pairs are semicolons or commas as delimiters. The peak list ofan example has therefore the form: δ₁ (intensity₁); δ₂ (intensity₂); . .. ; δ_(i) (intensity_(i)); . . . ; δ_(n) (intensity_(n)) or δ₁(intensity₁), δ₂ (intensity₂), . . . ; δ_(i) (intensity_(i)), . . . .δ_(n) (intensity_(n)) Intensity of sharp signals correlates with theheight of the signals in a printed example of a NMR spectrum in cm andshows the real relations of signal intensities. From broad signalsseveral peaks or the middle of the signal and their relative intensityin comparison to the most intensive signal in the spectrum can be shown.For calibrating chemical shift for ¹H spectra, we use tetramethylsilaneand/or the chemical shift of the solvent used, especially in the case ofspectra measured in DMSO. Therefore in NMR peak lists, tetramethylsilanepeak can occur but not necessarily. The ¹H-NMR peak lists are similar toclassical ¹H-NMR prints and contains therefore usually all peaks, whichare listed at classical NMR- interpretation. Additionally they can showlike classical ¹H-NMR prints signals of solvents, stereoisomers of thetarget compounds, which are also object of the invention, and/or peaksof impurities. To show compound signals in the delta-range of solventsand/or water the usual peaks of solvents, for example peaks of DMSO inDMSO-D₆ and the peak of water are shown in our ¹H-NMR peak lists andhave usually on average a high intensity. The peaks of stereoisomers ofthe target compounds and/or peaks of impurities have usually on averagea lower intensity than the peaks of target compounds (for example with apurity >90%). Such stereoisomers and/or impurities can be typical forthe specific preparation process. Therefore their peaks can help torecognize the reproduction of our preparation process via“side-products-fingerprints”. An expert, who calculates the peaks of thetarget compounds with known methods (MestreC, ACD-simulation, but alsowith empirically evaluated expectation values) can isolate the peaks ofthe target compounds as needed optionally using additional intensityfilters. This isolation would be similar to relevant peak picking atclassical ¹H-NMR interpretation. Further details of NMR-data descriptionwith peak lists you find in the publication “Citation of NMR PeaklistData within Patent Applications” of the Research Disclosure DatabaseNumber 564025. Ex- am- logP LC-MS ple (Method (Method No L0) ^([a])L2-L5) NMR or NMR Peaklist 1 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (4.41), 0.008 (4.06), L1): 2.342 (16.00), 2.759(1.07), 7.059 (1.60), Rt = 1.42 7.111 (0.66), 7.128 (1.05), 7.183(4.61), min; MS 7.195 (1.69), 7.202 (0.82), 7.207 (0.96), (ESIpos):7.422 (0.89), 7.438 (0.75), 7.855 (4.02), m/z = 440 7.865 (2.24), 7.869(2.26), 8.303 (1.26), [M + H]+ 8.314 (1.10), 8.317 (1.07), 8.328 (1.10),8.874 (5.11), 9.102 (0.96), 9.123 (0.96). 2 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: −0.008 (3.38), 1.805 (1.14), L1): 1.836(2.05), 1.854 (1.44), 1.862 (1.41), Rt = 1.47 1.867 (1.25), 1.879(1.41), 1.887 (1.60), min; MS 1.910 (1.44), 1.932 (1.44), 1.946 (1.07),(ESIpos): 1.960 (0.93), 2.045 (1.14), 2.069 (1.54), m/z = 481 2.080(1.05), 2.088 (1.03), 2.746 (1.96), [M + H]+ 2.760 (3.98), 2.771 (3.46),2.787 (1.53), 3.289 (3.24), 5.230 (0.89), 5.248 (1.82), 5.265 (1.70),5.281 (0.81), 7.111 (2.30), 7.128 (3.40), 7.161 (1.10), 7.166 (1.44),7.179 (3.34), 7.184 (3.63), 7.190 (3.11), 7.196 (4.53), 7.202 (2.62),7.208 (2.92), 7.212 (2.70), 7.226 (0.95), 7.422 (3.20), 7.439 (2.63),7.444 (2.24), 7.675 (7.89), 7.679 (16.00), 7.683 (9.38), 7.687 (5.20),7.692 (1.77), 7.889 (2.30), 7.907 (3.45), 7.909 (4.06), 7.928 (3.18),7.999 (3.67), 8.002 (4.95), 8.017 (2.68), 8.020 (3.30), 8.383 (3.21),8.386 (4.14), 8.404 (2.94), 8.407 (3.59), 8.940 (10.21), 9.119 (3.46),9.141 (3.28). 3 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:0.008 (1.33), 1.234 (2.20), 1.397 L1): (0.85), 1.924 (1.63), 1.935(0.83), 1.946 Rt = 1.37 (1.76), 1.956 (1.90), 1.967 (0.79), 1.977 min;MS (1.84), 1.998 (0.66), 2.524 (2.18), 2.567 (ESIpos): (0.88), 2.575(0.77), 2.838 (0.77), 2.859 m/z = 467 (1.28), 2.878 (2.28), 2.898(2.50), 2.918 [M + H]+ (1.19), 2.951 (1.54), 2.959 (1.64), 2.973 (1.71),2.980 (1.81), 2.990 (0.99), 2.999 (0.88), 3.012 (0.86), 3.020 (0.74),3.070 (1.91), 5.542 (1.02), 5.562 (2.83), 5.582 (2.79), 5.602 (0.92),7.223 (0.96), 7.232 (4.00), 7.240 (4.95), 7.246 (5.24), 7.254 (7.15),7.263 (2.96), 7.271 (3.67), 7.281 (2.50), 7.293 (1.17), 7.435 (2.55),7.446 (2.61), 7.456 (2.00), 7.635 (1.10), 7.665 (0.98), 7.678 (13.08),7.681 (16.00), 7.686 (7.10), 7.689 (3.73), 7.695 (1.37), 7.700 (0.80),7.895 (2.06), 7.913 (4.25), 7.934 (3.06), 8.004 (4.66), 8.008 (3.27),8.022 (3.28), 8.026 (2.07), 8.393 (4.14), 8.396 (2.75), 8.414 (3.73),8.417 (2.39), 8.962 (10.00), 9.118 (3.31), 9.139 (3.23). 4 LC-MS ¹H-NMR(400 MHz, DMSO-d6) delta (Method [ppm]: 0.008 (2.60), 0.833 (1.52),0.839 L1): (3.28), 0.855 (3.89), 0.859 (2.26), 0.871 Rt = 1.33 (1.10),0.876 (0.82), 1.106 (9.55), 1.157 min; MS (1.22), 1.175 (2.15), 1.193(1.15), 1.988 (ESIpos): (3.86), 2.058 (0.88), 2.066 (0.96), 2.076 m/z =483 (1.10), 2.086 (2.40), 2.093 (1.49), 2.100 [M + H]+ (1.27), 2.109(0.88), 2.196 (0.93), 2.208 (1.32), 2.221 (1.22), 2.229 (1.16), 2.243(0.82), 3.076 (2.73), 3.288 (3.01), 4.021 (0.91), 4.038 (0.91), 4.221(0.77), 4.241 (2.10), 4.249 (1.66), 4.261 (2.02), 4.270 (2.60), 4.279(2.07), 4.287 (1.71), 4.296 (1.82), 5.266 (0.85), 5.281 (1.90), 5.301(1.91), 5.315 (0.88), 6.789 (3.17), 6.791 (3.20), 6.809 (3.59), 6.812(3.55), 6.916 (1.71), 6.918 (1.65), 6.934 (3.51), 6.937 (3.37), 6.953(2.16), 6.956 (1.99), 7.157 (1.74), 7.162 (1.79), 7.179 (2.96), 7.196(1.43), 7.200 (1.40), 7.379 (3.11), 7.398 (2.90), 7.676 (7.53), 7.680(16.00), 7.685 (7.22), 7.688 (4.08), 7.694 (1.49), 7.893 (2.34), 7.911(3.81), 7.914 (3.22), 7.932 (3.47), 8.006 (4.05), 8.010 (4.08), 8.024(3.07), 8.027 (2.79), 8.387 (3.53), 8.390 (3.48), 8.408 (3.33), 8.411(3.06). 8.962 (10.68), 9.251 (3.18), 9.272 (3.11), 5 LC-MS ¹H-NMR (400MHz, DMSO-d6) delta (Method [ppm]: −0.008 (3.48), 0.008 (3.53), L1):1.157 (0.87), 1.175 (1.69), 1.192 (0.90), Rt = 1.24 1.988 (2.96), 2.058(0.97), 2.066 (1.02), min; MS 2.075 (1.14), 2.082 (1.14), 2.093 (1.62),(ESIpos): 2.100 (1.34), 2.108 (0.97), 2.196 (1.00), m/z = 449 2.209(1.44), 2.222 (1.34), 2.231 (1.27), [M + H]+ 3.289 (3.14), 4.021 (0.70),4.038 (0.70), 4.221 (0.87), 4.241 (2.39), 4.249 (1.84), 4.261 (2.26),4.269 (2.89), 4.279 (2.24), 4.287 (1.79), 4.296 (2.04), 5.268 (0.95),5.282 (2.07), 5.302 (2.07), 5.318 (0.95), 6.788 (3.63), 6.791 (4.03),6.809 (4.26), 6.811 (4.43), 6.915 (2.02), 6.918 (2.07), 6.934 (4.08),6.937 (4.13), 6.952 (2.54), 6.956 (2.41), 7.157 (2.04), 7.161 (2.19),7.178 (3.28), 7.196 (1.67), 7.200 (1.59), 7.378 (3.31), 7.398 (3.16),7.491 (1.37), 7.496 (1.05), 7.506 (3.83), 7.510 (10.25), 7.515 (4.63),7.529 (6.47), 7.549 (2.34), 7.572 (3.11), 7.577 (5.20), 7.581 (2.86),7.589 (1.84), 7.593 (2.59), 7.598 (1.67), 7.675 (2.91), 7.679 (6.05),7.684 (3.38), 7.887 (2.84), 7.905 (4.85), 7.908 (3.73), 7.926 (5.13),7.958 (5.28), 7.962 (5.82), 7.976 (3.31), 7.979 (2.86), 8.362 (4.30),8.366 (4.45), 8.383 (4.11), 8.387 (3.83), 8.934 (16.00), 9.244 (3.56),9.265 (3.46). 6 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.008 (3.23), 0.008 (3.14), 0.853 L1): (0.88), 1.175 (2.40), 1.235(4.21), 1.925 Rt = 1.31 (1.92), 1.934 (0.91), 1.945 (1.99), 1.956 min;MS (2.12), 1.967 (0.92), 1.976 (2.11), 1.998 (ESIpos): (0.79), 2.517(2.33), 2.525 (2.38), 2.568 m/z = 433 (0.89), 2.859 (1.26), 2.878(1.91), 2.899 [M + H]+ (2.60), 2.919 (1.22), 2.951 (1.61), 2.959 (1.75),2.973 (1.77), 2.981 (1.65), 2.990 (0.94), 2.999 (0.87), 3.287 (2.04),5.544 (1.02), 5.564 (3.03), 5.584 (3.00), 5.604 (0.98), 5.754 (7.31),6.510 (1.69), 7.232 (5.18), 7.241 (5.18), 7.246 (6.49), 7.255 (9.27),7.264 (2.87), 7.272 (3.87), 7.281 (2.34), 7.285 (1.99), 7.294 (1.18),7.434 (2.78), 7.447 (2.68), 7.456 (2.20), 7.488 (0.77), 7.492 (1.58),7.497 (1.25), 7.507 (4.17), 7.512 (9.71), 7.515 (6.13), 7.517 (5.24),7.531 (6.56), 7.551 (2.46), 7.574 (3.40), 7.579 (5.63), 7.584 (3.06),7.592 (1.94), 7.596 (2.78), 7.601 (1.72), 7.676 (3.20), 7.678 (3.96),7.680 (6.36), 7.685 (3.54), 7.889 (3.03), 7.907 (5.37), 7.910 (3.81),7.928 (5.57), 7.957 (5.81), 7.961 (6.39), 7.975 (3.50), 7.979 (2.97),8.368 (4.68), 8.372 (4.77), 8.389 (4.45), 8.393 (4.06), 8.935 (16.00),9.113 (3.64), 9.134 (3.51). 7 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: 0.008 (3.31), 0.852 (0.82), 1.142 L1): (0.91), 1.157(1.29), 1.172 (2.28), 1.175 Rt = 1.24 (2.52), 1.192 (1.46), 1.234(5.59), 1.394 min; MS (15.65), 1.398 (16.00), 1.985 (3.80), (ESIpos):1.988 (4.30), 2.039 (2.93), 2.046 (3.13), m/z = 483 2.057 (3.86), 2.064(3.92), 2.074 (5.03), [M + H]+ 2.082 (7.46), 2.086 (6.64), 2.090 (3.57),2.098 (2.57), 2.185 (3.22), 2.196 (4.56), 2.207 (4.45), 2.218 (4.15),2.230 (3.16), 2.242 (2.40), 2.251 (1.61), 2.365 (0.76), 2.707 (0.88),3.288 (5.56), 4.020 (1.05), 4.038 (1.02), 4.204 (2.11), 4.232 (5.79),4.259 (7.69), 4.268 (7.31), 4.276 (6.03), 4.285 (6.49), 4.296 (2.90),4.304 (2.52), 4.312 (1.99), 5.251 (2.66), 5.266 (6.52), 5.285 (7.14),5.300 (3.71), 6.781 (12.26), 6.788 (2.84), 6.801 (13.54), 6.809 (3.01),6.903 (5.41), 6.922 (11.79), 6.940 (7.05), 6.953 (1.43), 7.150 (6.38),7.170 (10.21), 7.189 (4.94), 7.363 (10.65), 7.383 (15.97), 7.403(10.71), 7.456 (7.17), 7.475 (11.58), 7.495 (5.62), 7.511 (3.80), 7.528(2.19), 7.548 (0.88), 7.573 (1.93), 7.590 (1.14), 7.677 (2.72), 7.720(7.52), 7.723 (13.02), 7.727 (7.34), 7.740 (6.82), 7.743 (11.14), 7.747(6.20), 7.845 (5.00), 7.849 (8.98), 7.852 (5.56), 7.863 (9.83), 7.866(15.94), 7.870 (9.04), 7.883 (1.11), 7.898 (8.89), 7.902 (9.54), 7.919(13.05), 7.923 (10.44), 7.937 (5.59), 7.940 (5.21), 7.958 (2.72), 7.976(1.43), 8.362 (2.05), 8.383 (2.05), 8.397 (12.37), 8.418 (11.26), 8.854(13.98), 8.860 (14.48), 8.932 (4.65), 9.245 (6.76), 9.254 (6.38), 9.266(7.08), 9.275 (5.79). 8 2.53 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (1.11), 0.008 (1.00), 3.066 L6): (16.00), 3.071(4.46), 3.287 (1.77), 3.926 Rt = 2.06 (1.28), 4.269 (0.87), 6.785(0.90), 6.788 min; MS (0.97), 6.805 (1.03), 6.808 (1.03), 6.925(ESIpos): (0.97), 6.928 (0.93), 6.944 (0.61), 6.947 m/z = 492 (0.58),7.171 (0.77), 7.359 (0.80), 7.378 [M + H]+ (0.74), 7.629 (1.51), 7.634(12.99), 7.647 (1.14), 7.650 (0.96), 7.668 (0.99), 7.790 (1.13), 7.793(1.20), 7.807 (0.93), 7.811 (0.88), 8.229 (1.01), 8.233 (1.03), 8.251(0.94), 8.254 (0.89), 8.632 (3.95), 9.084 (0.86), 9.105 (0.84). 9 LC-MS¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (2.94), 0.008(2.72), 2.323 L1): (0.52), 2.710 (0.57), 3.070 (16.00), 3.286 Rt = 1.04(4.49), 3.567 (0.42), 5.534 (0.73), 7.220 min; MS (1.05), 7.235 (1.05),7.242 (1.91), 7.267 (ESIpos): (0.89), 7.630 (1.27), 7.636 (12.76), 7.648m/z = 476 (1.00), 7.670 (0.93), 7.788 (1.11), 7.792 [M + H]+ (1.16),7.806 (0.97), 8.232 (1.08), 8.253 (0.95), 8.638 (4.07), 8.941 (0.86),8.962 (0.79). 10 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.008 (1.60), 0.008 (1.51), L6): 2.326 (13.07), 3.055 (16.00), 3.288 Rt= 1.69 (3.31), 6.784 (0.87), 6.787 (0.96), 6.804 min; MS (1.02), 6.807(1.05), 6.922 (0.96), 6.925 (ESIpos): (0.93), 6.940 (0.61), 6.943(0.58), 7.009 m/z = 476 (1.28), 7.147 (3.19), 7.584 (0.61), 7.601 [M +H]+ (1.16), 7.604 (0.75), 7.622 (1.25), 7.640 (1.28), 7.645 (1.45),7.658 (0.73), 8.150 (0.99), 8.154 (0.99), 8.170 (0.93), 8.175 (0.84),8.581 (4.01), 9.069 (0.84), 9.090 (0.81). 11 LC-MS ¹H-NMR (500 MHz,DMSO-d6) delta (Method [ppm]: −0.007 (1.04), 0.007 (1.04), 2.568 L7):(6.31), 3.046 (16.00), 3.286 (1.53), 5.532 Rt = 2.58 (0.72), 5.548(0.72), 7.220 (1.16), 7.224 min; MS (0.84), 7.228 (1.19), 7.233 (1.07),7.238 (ESIpos): (1.68), 7.266 (0.89), 7.403 (0.73), 7.623 m/z = 490(0.69), 7.627 (1.62), 7.631 (1.75), 7.641 [M + H]+ (5.09), 7.645 (3.28),7.664 (1.62), 7.667 (1.70), 8.012 (1.49), 8.014 (1.50), 8.016 (1.25),8.578 (3.50), 8.934 (0.95), 8.951 (0.93). 12 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: −0.008 (3.00), 0.008 (2.59), 2.566 L6):(6.36), 3.042 (16.00), 3.287 (1.44), 4.270 Rt = 2.18 (0.90), 5.754(4.48), 6.785 (1.08), 6.806 min; MS (1.12), 6.923 (1.03), 6.942 (0.64),7.168 (ESIpos): (0.84), 7.351 (0.82), 7.371 (0.78), 7.621 m/z = 506(0.71), 7.626 (1.60), 7.630 (2.09), 7.639 [M + H]+ (6.13), 7.644 (3.08),7.665 (1.73), 7.670 (1.76), 8.012 (1.45), 8.572 (3.85), 9.076 (0.91),9.096 (0.91). 13 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.008 (1.31), 0.008 (1.23), 3.065 L1): (16.00), 4.270 (0.87), 6.785(0.94), 6.788 Rt = 1.05 (1.04), 6.806 (1.05), 6.809 (1.12), 6.926 min;MS (0.98), 6.929 (0.96), 6.944 (0.62), 7.171 (ESIpos): (0.78), 7.377(0.73), 7.628 (0.81), 7.646 m/z = 510 (1.07), 7.650 (0.98), 7.668(1.02), 7.802 [M + H]+ (4.91), 7.806 (1.58), 7.818 (4.35), 7.824 (1.06),8.227 (1.02), 8.231 (1.06), 8.249 (0.95), 8.252 (0.89), 8.636 (4.18),9.087 (0.78), 9.108 (0.78). 14 LC-MS ¹H-NMR (400 MHz, CHLOROFORM-d)(Method delta [ppm]: −0.008 (1.09), 0.008 (1.14), L7): 1.562 (5.12),2.082 (1.48), 2.090 (1.98), Rt = 2.39 2.098 (3.67), 2.107 (2.27), 2.116(1.78), min; MS 2.588 (16.00), 4.031 (2.54), 4.248 (1.04), (ESIpos):4.259 (1.53), 4.270 (1.04), 6.783 (0.82), m/z = 518 7.213 (0.97), 7.232(0.93), 7.348 (4.36), [M + H]+ 7.353 (5.19), 7.377 (0.81), 7.525 (1.06),7.530 (1.97), 7.535 (1.20), 7.571 (0.87), 7.590 (1.42), 7.611 (1.29),7.676 (1.58), 7.679 (1.69), 7.694 (1.17), 7.697 (1.10), 8.088 (1.16),8.171 (1.22), 8.193 (1.14). 15 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (1.60), 0.008 (1.51), 2.326 L6): (13.07), 3.055(16.00), 3.288 (3.31), Rt = 1.55 6.784 (0.87), 6.787 (0.96), 6.804(1.02), min; MS 6.807 (1.05), 6.922 (0.96), 6.925 (0.93), (ESIpos):6.940 (0.61), 6.943 (0.58), 7.009 (1.28), m/z = 452 7.147 (3.19), 7.584(0.61), 7.601 (1.16), [M + H]+ 7.604 (0.75), 7.622 (1.25), 7.640 (1.28),7.645 (1.45), 7.658 (0.73), 8.150 (0.99), 8.154 (0.99), 8.170 (0.93),8.175 16 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: 2.756(0.89), 2.770 (0.83), 3.070 L6): (16.00), 7.124 (0.88), 7.173 (0.86),7.177 Rt = 2.26 (0.86), 7.190 (1.17), 7.202 (0.75), 7.207 min; MS(0.69), 7.389 (0.77), 7.627 (1.23), 7.632 (ESIpos): (11.18), 7.645(1.08), 7.648 (0.95), 7.666 m/z = 490 (0.97), 7.783 (1.07), 7.787(1.17), 7.801 [M + H]+ (0.91), 7.805 (0.87), 8.228 (1.01), 8.232 (1.03),8.250 (0.94), 8.253 (0.90), 8.608 (3.86), 8.972 (0.87), 8.993 (0.85). 17LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (1.02),0.008 (0.92), 1.169 L1): (0.67), 3.268 (1.80), 3.280 (4.39), 3.287 Rt =1.24 (5.64), 3.865 (3.30), 3.877 (5.67), 3.889 min; MS (3.15), 4.244(1.15), 4.252 (0.88), 4.265 (ESIpos): (1.45), 4.276 (1.35), 4.283(0.98), 4.292 m/z = 534 (0.96), 5.255 (1.02), 5.275 (1.02), 6.786 [M +H]+ (1.88), 6.789 (2.08), 6.807 (2.18), 6.810 (2.27), 6.915 (1.06),6.918 (1.05), 6.934 (2.10), 6.937 (2.04), 6.952 (1.32), 6.955 (1.28),7.153 (1.06), 7.158 (1.11), 7.175 (1.66), 7.192 (0.85), 7.196 (0.84),7.380 (1.77), 7.399 (1.67), 7.633 (2.13), 7.636 (4.66), 7.639 (16.00),7.643 (3.34), 7.682 (1.63), 7.699 (2.18), 7.703 (1.97), 7.721 (2.07),7.830 (2.42), 7.834 (2.58), 7.848 (2.01), 7.851 (1.90), 8.276 (2.01),8.280 (2.07), 8.297 (1.93), 8.301 (1.76), 8.699 (8.76), 9.164 (1.90),9.184 (1.86). 18 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.008 (2.30), 0.008 (2.10), 2.037 L6): (0.83), 2.168 (0.72), 2.180(0.72), 2.262 Rt = 1.77 (16.00), 3.070 (2.04), 4.217 (0.95), 4.243 min;MS (1.45), 4.252 (1.36), 4.259 (1.09), 4.268 (ESIpos): (1.06), 5.207(0.94), 5.226 (0.92), 6.779 m/z = 506 (1.82), 6.800 (1.99), 6.881(1.11), 6.884 [M + H]+ (1.13), 6.900 (2.29), 6.903 (2.22), 6.919 (1.39),6.922 (1.31), 7.140 (0.97), 7.144 (1.05), 7.161 (1.67), 7.179 (0.84),7.183 (0.82), 7.323 (2.16), 7.343 (1.95), 7.569 (0.80). 19 LC-MS ¹H-NMR(400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (1.93), 0.008 (1.79),1.879 L6): (0.89), 1.899 (0.96), 1.908 (1.37), 1.930 Rt = 1.81 (1.00),2.261 (16.00), 2.832 (0.71), 2.851 min; MS (0.96), 2.871 (1.31), 2.940(0.83), 2.949 (ESIpos): (0.89), 2.962 (0.93), 2.971 (0.90), 3.081 m/z =490 (2.10), 5.500 (1.37), 5.520 (1.38), 7.201 [M + H]+ (1.33), 7.207(2.03), 7.215 (3.05), 7.223 (2.67), 7.230 (2.32), 7.243 (0.97), 7.248(0.89), 7.258 (2.20), 7.274 (1.48), 7.280 (1.39), 7.361 (1.57), 7.368(1.60), 7.383 (1.37), 7.546 (0.94), 7.568 (1.01). 20 LC-MS ¹H-NMR (400MHz, DMSO-d6) delta (Method [ppm]: 1.149 (1.09), 1.837 (2.38), L1):2.069 (1.99), 2.757 (4.80), 3.878 (12.72), Rt = 1.32 5.231 (2.34), 7.125(3.98), 7.180 (3.90), min; MS 7.197 (4.92), 7.213 (3.63), 7.411 (3.59),(ESIpos): 7.428 (3.24), 7.636 (16.00), 7.680 (2.42), m/z =532 7.698(3.79), 7.718 (2.69), 7.826 (4.25), [M + H]+ 7.842 (3.43), 8.280 (3.71),8.300 (3.40), 8.673 (8.04), 9.047 (3.28), 9.067 (3.16). 21 LC-MS ¹H-NMR(400 MHz, DMSO-d6) delta (Method [ppm]: 3.071 (16.00), 5.515 (0.74),L1): 5.535 (0.74), 7.213 (1.11), 7.222 (1.33), Rt = 1.20 7.230 (1.61),7.234 (1.34), 7.261 (0.99), min; MS 7.381 (0.72), 7.389 (0.77), 7.495(2.53), (ESIpos): 7.500 (2.65), 7.584 (0.68), 7.607 (1.36), m/z = 4947.630 (0.72), 7.679 (0.71), 7.684 (1.25), [M + H]+ 7.689 (0.68), 8.280(0.72), 8.295 (0.78), 8.304 (0.76), 8.319 (0.70), 8.607 (3.29), 8.927(0.97), 8.948 (0.95). 22 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method[ppm]: 3.067 (16.00), 4.249 (0.91), L6): 4.258 (0.94), 6.779 (0.92),6.782 (1.01), Rt = 2.26 6.800 (1.06), 6.803 (1.10), 6.912 (1.02), min;MS 6.915 (1.03), 6.931 (0.61), 7.165 (0.86), (ESIpos): 7.339 (0.87),7.358 (0.82), 7.494 (2.71), m/z = 510 7.499 (2.71), 7.584 (0.72), 7.607(1.42), [M + H]+ 7.630 (0.77), 7.677 (0.88), 7.682 (1.54), 7.687 (0.82),8.278 (0.75), 8.294 (0.81), 8.302 (0.81), 8.318 (0.73), 8.600 (3.49),9.066 (0.94), 9.087 (0.93). 23 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.149 (1.58), −0.008 (15.27), L1): 0.008 (13.12), 0.146(1.58), 2.154 (1.98), Rt = 0:8/ 2.367 (2.04), 2.709 (1.98), 3.054(12.95), min; MS 3.067 (11.82), 3.288 (8.82), 4.260 (5.48), (ESIpos):5.250 (2.09), 6.782 (4.01), 6.803 (4.13), m/z = 496 6.895 (1.92), 6.910(3.67), 6.928 (2.37), [M + H]+ 7.160 (2.83), 7.308 (3.11), 7.325 (2.94),7.517 (2.49), 7.535 (3.73), 7.556 (3.00), 7.732 (4.18), 7.746 (3.45),7.784 (14.53), 7.801 (16.00), 8.339 (3.17), 8.360 (3.05), 8.453 (11.82),8.966 (3.17), 8.987 (3.22). 24 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.149 (1.23), −0.008 (10.75), L1): 0.008 (11.29), 0.146(1.26), 0.850 (1.36), Rt = 0:86 0.868 (0.82), 2.046 (1.11), 2.061(1.08), min; MS 2.140 (1.17), 2.154 (1.33), 3.055 (9.80), (ESIpos):3.067 (9.17), 3.287 (3.23), 4.246 (2.43), m/z = 478 4.259 (4.02), 4.274(2.37), 5.230 (1.36), [M + H]+ 5.250 (1.39), 6.778 (2.53), 6.781 (2.78),6.799 (2.91), 6.802 (3.04), 6.891 (1.39), 6.894 (1.42), 6.909 (2.75),6.912 (2.81), 6.928 (1.71), 6.931 (1.74), 7.140 (1.36), 7.144 (1.49),7.161 (2.21), 7.179 (1.14), 7.183 (1.17), 7.305 (2.15), 7.324 (2.09),7.516 (2.06), 7.534 (2.62), 7.537 (2.50), 7.555 (2.43), 7.595 (1.71),7.599 (3.98), 7.604 (4.93), 7.615 (16.00), 7.620 (9.01), 7.713 (3.07),7.716 (3.35), 7.730 (2.69), 7.734 (2.59), 7.792 (1.55), 7.805 (1.49),8.336 (2.21), 8.340 (2.40), 8.358 (2.25), 8.362 (2.18), 8.446 (9.01),8.968 (2.50), 8.989 (2.43). 25 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: 3.282 (1.79), 3.293 (1.98), 3.311 L1): (16.00), 6.807(0.71), 6.932 (0.68), 7.468 Rt = 1.08 (0.89), 7.474 (0.85), 7.493(0.76), 7.540 min; MS (0.71), 7.643 (0.98), 7.780 (0.75), 8.673(ESIpos): (1.65). m/z = 500 [M + H]+ 26 LC-MS ¹H-NMR (400 MHz, DMSO-d6)delta (Method [ppm]: −0.008 (4.85), 0.008 (4.19), L1): 1.234 (0.78),1.710 (0.76), 1.740 (0.93), Rt = 1.07 1.986 (1.09), 1.999 (1.07), 2.007(1.05), min; MS 2.021 (0.85), 2.072 (1.71), 2.366 (0.62), (ESIpos):2.709 (0.62), 3.287 (4.75), 3.971 (0.74), m/z = 515 3.977 (0.87), 3.999(1.86), 4.006 (1.18), [M + H]+ 4.021 (1.22), 4.027 (0.93), 4.132 (0.93),4.139 (1.24), 4.149 (1.14), 4.158 (1.40), 4.168 (0.85), 4.176 (0.89),4.185 (0.68), 5.041 (0.74), 5.055 (1.65), 5.074 (1.65), 5.088 (0.72),6.741 (3.06), 6.761 (3.39), 6.837 (1.45), 6.840 (1.45), 6.856 (3.14),6.874 (1.94), 7.020 (2.31), 7.039 (1.88), 7.122 (1.63), 7.126 (1.53),7.142 (2.64), 7.160 (1.30), 7.164 (1.22), 7.264 (5.35), 7.499 (5.93),7.502 (6.65), 7.519 (3.45), 7.523 (3.34), 7.700 (5.90), 7.703 (16.00),7.802 (2.44), 7.820 (3.22), 7.841 (2.46), 7.917 (3.72), 8.008 (3.14),8.011 (3.53), 8.027 (2.79), 8.030 (2.85), 8.962 (2.87), 8.982 (2.79),9.152 (10.38). 27 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] =12.73 (br s, 1H), 9.01 (d, 1H), L1): 8.69 (s, 1H), 8.46 (d, 1H), 8.30(br d, 1H), Rt = 1.06 8.13 (s, 1H), 7.75 (d, 1H), 7.69 (s, 1H), min; MS7.41-7.62 (m, 4H), 7.07-7.36 (m, 8H), (ESIpos): 5.39-5.60 (m, 2H),2.90-3.07 (m, 2H), m/z = 530 2.73-2.88 (m, 2H), 2.57-2.69 (m, 1H), [M +H]+ 2.53-2.71 (m, 13H), 2.30-2.44 (m, 1H), 2.09 (dq, 1H), 1.93 (dq, 1H).28 LC-MS (Method L1): Rt = 1.09 min; MS (ESIpos): m/z = 564 [M + H]+ 29LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: 3.072 (16.00),3.287 (1.21), 5.754 L1): (0.68), 6.774 (0.89), 6.777 (0.93), 6.794 Rt =0.88 (1.01), 6.797 (0.99), 6.905 (0.97), 6.908 min; MS (0.91), 6.923(0.62), 7.303 (0.79), 7.311 (ESIpos): (0.71), 7.324 (0.64), 7.332(1.23), 7.579 m/z = 476 (0.65), 7.633 (3.39), 7.641 (1.60), 7.651 [M +H]+ (1.51), 8.240 (1.01), 8.247 (0.94), 8.258 (0.82), 8.265 (0.85),8.531 (4.23), 9.073 (0.80), 9.093 (0.77). 30 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: −0.008 (0.71), 3.063 (16.00), L1): 4.262(0.82), 4.270 (0.92), 6.784 (0.87), Rt = 0.88 6.787 (0.95), 6.805(1.03), 6.808 (1.04), min; MS 6.924 (0.98), 6.927 (0.96), 6.943 (0.63),(ESIpos): 6.946 (0.58), 7.171 (0.79), 7.351 (0.81), m/z = 460 7.370(0.78), 7.496 (0.70), 7.523 (0.72), [M + H]+ 7.620 (0.81), 7.637 (1.13),7.641 (1.00), 7.659 (1.13), 7.751 (1.16), 7.754 (1.21), 7.768 (0.93),7.772 (0.86), 8.201 (1.03), 8.205 (1.05), 8.222 (0.98), 8.226 (0.90),8.613 (3.83), 9.077 (0.87), 9.097 (0.85). 31 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: 3.059 (16.00), 3.287 (0.75), 3.855 L1):(10.21), 4.263 (0.81), 4.271 (0.92), 6.785 Rt = 0.83 (0.89), 6.788(1.00), 6.806 (1.02), 6.808 min; MS (1.10), 6.923 (0.99), 6.926 (1.02),6.942 (ESIpos): (0.60), 7.143 (0.67), 7.149 (1.06), 7.154 m/z = 472(1.00), 7.171 (0.85), 7.244 (0.97), 7.265 [M + H]+ (0.76), 7.273 (0.99),7.294 (0.73), 7.344 (0.93), 7.349 (1.64), 7.366 (1.32), 7.370 (1.57),7.607 (0.73), 7.625 (1.04), 7.628 (0.92), 7.646 (1.00), 7.731 (1.12),7.735 (1.21), 7.749 (0.87), 7.752 (0.84), 8.176 (0.99), 8.180 (1.04),8.197 (0.93), 8.201 (0.91), 8.600 (3.83), 9.082 (0.91), 9.103 (0.89). 32LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (1.08),0.008 (1.10), 3.069 L1): (16.00), 3.944 (7.95), 4.253 (0.96), 4.262 Rt =0.87 (1.04), 6.777 (1.03), 6.781 (1.18), 6.798 min; MS (1.20), 6.801(1.26), 6.894 (0.57), 6.897 (ESIpos): (0.59), 6.912 (1.14), 6.915(1.14), 6.931 m/z = 490 (0.70), 6.934 (0.68), 7.116 (0.62), 7.131 [M +H]+ (0.71), 7.134 (0.70), 7.146 (0.75), 7.163 (0.92), 7.186 (0.84),7.213 (0.89), 7.339 (0.92), 7.358 (0.88), 7.623 (0.67), 7.641 (1.36),7.643 (0.86), 7.661 (1.47), 7.675 (1.33), 7.679 (1.50), 7.692 (0.67),8.235 (1.06), 8.239 (1.07), 8.255 (1.01), 8.260 (0.92), 8.549 (4.05),9.070 (1.00), 9.091 (0.97). 33 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: 1.819 (1.63), 1.835 (1.55), 3.072 L1): (16.00), 4.248(0.89), 4.257 (0.93), 6.777 Rt = 0.84 (0.92), 6.798 (1.00), 6.904(0.81), 7.160 min; MS (1.13), 7.181 (0.99), 7.184 (0.91), 7.328(ESIpos): (0.83), 7.347 (0.76), 7.558 (0.73), 7.562 m/z = 456 (0.79),7.576 (1.27), 7.579 (1.20), 7.618 [M + H]+ (1.09), 7.635 (0.76), 7.639(1.15), 7.656 (0.69), 8.216 (1.00), 8.220 (1.05), 8.237 (0.92), 8.241(0.89), 8.521 (3.83). 34 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method[ppm]: −0.008 (0.91), 0.008 (0.91), 3.074 L1); (16.00), 3.287 (1.06),4.248 (0.91), 4.255 Rt = 0.93 (1.07), 6.771 (1.09), 6.774 (1.20), 6.792min; MS (1.29), 6.795 (1.32), 6.903 (1.12), 6.922 (ESIpos): (0.67),7.140 (0.60), 7.156 (0.93), 7.324 m/z = 492 (1.17), 7.328 (1.10), 7.343(1.08), 7.347 [M + H]+ (1.14), 7.426 (0.79), 7.437 (0.86), 7.628 (1.83),7.632 (3.18), 7.651 (1.79), 7.669 (0.69), 7.675 (1.55), 7.679 (1.60),7.695 (1.35), 7.699 (1.26), 8.240 (1.22), 8.246 (1.24), 8.259 (1.08),8.265 (1.09), 8.520 (2.86). 35 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (3.10), 0.008 (2.86), L1): 1.147 (0.97), 1.920(1.70), 1.930 (0.91), Rt = 1.12 1.940 (1.83), 1.952 (1.95), 1.961(0.97), min; MS 1.971 (1.89), 1.993 (0.73), 2.366 (2.43), (ESIpos):2.525 (6.69), 2.566 (2.62), 2.710 (2.49), m/z = 484 2.831 (0.79), 2.852(1.52), 2.871 (2.01), [M + H]+ 2.891 (2.68), 2.911 (1.22), 2.963 (1.58),2.972 (1.70), 2.985 (1.70), 2.994 (1.64), 3.002 (1.03), 3.012 (0.91),3.024 (0.91), 3.033 (0.79), 3.288 (15.21), 3.297 (13.02), 3.859 (8.40),3.871 (12.35), 3.882 (7.85), 5.524 (1.03), 5.543 (3.04), 5.563 (3.04),5.582 (1.03), 7.226 (5.23), 7.234 (5.60), 7.240 (6.14), 7.248 (9.06),7.258 (2.62), 7.270 (4.02), 7.279 (2.43), 7.292 (1.40), 7.420 (2.92),7.429 (2.92), 7.442 (2.56), 7.451 (2.31), 7.456 (1.58), 7.466 (3.71),7.471 (6.39), 7.476 (4.68), 7.479 (4.87), 7.497 (6.69), 7.516 (3.10),7.538 (3.41), 7.542 (5.84), 7.547 (3.29), 7.556 (1.89), 7.560 (3.10),7.565 (1.64), 7.640 (4.26), 7.644 (6.69), 7.649 (3.89), 7.675 (2.92),7.693 (4.50), 7.696 (3.83), 7.714 (4.26), 7.777 (5.05), 7.781 (5.23),7.795 (3.71), 7.799 (3.35), 8.255 (4.14), 8.258 (4.14), 8.276 (3.95),8.279 (3.65), 8.675 (16.00), 9.020 (4.02), 9.041 (3.89). 36 LC-MS ¹H-NMR(400 MHz, DMSO-d6) delta (Method [ppm]: −0.149 (0.70), −0.008 (6.82),L1): 0.008 (6.40), 0.146 (0.83), 1.147 (1.53), Rt = 0.86 1.926 (4.03),1.947 (3.76), 2.328 (1.25), min; MS 2.366 (2.09), 2.665 (1.11), 2.670(1.25), (ESIpos): 2.710 (2.09), 3.072 (16.00), 3.289 m/z = 472 (10.16),4.248 (1.11), 5.225 (0.56), 6.775 [M + H]+ (1.11), 6.796 (1.25), 6.903(0.83), 7.131 (1.11), 7.159 (1.11), 7.263 (0.83), 7.328 (0.97), 7.346(0.83), 7.461 (1.25), 7.481 (0.97), 7.564 (0.97), 7.578 (1.39), 7.582(1.39), 7.619 (1.11), 7.640 (1.25), 7.658 (0.70), 8.216 (1.11), 8.518(4.31), 9.058 (0.56). 37 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method[ppm]: −0.008 (3.91), 0.008 (3.78), 1.147 L1): (0.96), 2.019 (0.89),2.028 (1.03), 2.047 Rt = 0.90 (0.96), 2.055 (1.51), 2.062 (1.30), 2.070min; MS (0.89), 2.170 (0.96), 2.182 (1.30), 2.194 (ESIpos): (1.30),2.204 (1.17), 2.327 (0.69), 2.366 m/z = 476 (1.44), 2.665 (0.55), 2.669(0.76), 2.674 [M + H]+ (0.55), 2.710 (1.51), 3.081 (16.00), 4.212(0.69), 4.232 (2.20), 4.240 (1.85), 4.252 (3.50), 4.261 (3.64), 4.268(2.06), 4.277 (1.99), 4.295 (0.69), 5.218 (0.89), 5.232 (1.92), 5.252(1.85), 5.266 (0.82), 6.778 (3.50), 6.781 (3.85), 6.799 (4.05), 6.802(4.26), 6.894 (2.06), 6.897 (2.06), 6.912 (3.98), 6.915 (3.98), 6.931(2.61), 6.934 (2.40), 7.143 (1.99), 7.147 (2.06), 7.164 (3.09), 7.182(1.65), 7.186 (1.58), 7.319 (1.65), 7.341 (6.59), 7.364 (4.74), 7.480(1.51), 7.487 (2.06), 7.495 (1.72), 7.502 (2.27), 7.518 (1.72), 7.528(1.30), 7.540 (1.30), 7.636 (2.33), 7.654 (3.71), 7.657 (2.95), 7.675(3.57), 7.730 (3.16), 7.745 (2.06), 8.257 (2.47), 8.277 (2.33), 8.550(5.15), 9.077 (2.61), 9.097 (2.61). 38 LC-MS ¹H-NMR (400 MHz, DMSO-d6)delta (Method [ppm]: −0.149 (1.49), −0.008 (13.57), L6): 0.008 (12.78),0.146 (1.49), 1.147 (1.73), Rt = 1.80 2.199 (0.78), 2.327 (1.25), 2.366(1.88), min; MS 2.669 (1.41), 2.710 (1.88), 3.043 (1.65), (ESIpos):3.079 (16.00), 3.287 (12.86), 3.611 m/z = 508 (0.63), 3.906 (4.16),3.922 (4.16), 4.249 [M + H]+ (0.78), 5.247 (0.71), 6.777 (1.10), 6.798(1.18), 6.911 (0.94), 7.160 (0.86), 7.355 (1.18), 7.651 (0.71), 7.669(1.02), 7.690 (1.18), 7.752 (1.25), 8.280 (1.02), 8.302 (0.94), 8.544(4.00). 39 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008(0.97), 0.008 (0.99), 3.043 L1): (0.70), 3.071 (16.00), 3.289 (2.25),4.241 Rt = 0.94 (0.92), 4.250 (0.99), 6.769 (1.02), 6.772 min; MS(1.12), 6.789 (1.19), 6.792 (1.24), 6.877 (ESIpos): (0.58), 6.896(1.12), 6.914 (0.70), 7.137 m/z = 526 (0.61), 7.154 (0.92), 7.318(0.87), 7.339 [M + H]+ (1.14), 7.361 (0.68), 7.374 (0.75), 7.394 (0.75),7.597 (1.38), 7.604 (2.28), 7.624 (1.55), 7.641 (0.61), 7.776 (0.75),7.894 (0.85), 7.899 (0.85), 7.904 (0.85), 7.910 (0.73), 8.233 (1.09),8.239 (1.09), 8.253 (0.97), 8.258 (0.95), 8.473 (2.47), 8.476 (2.79),9.074 (0.75), 9.094 (0.70). 40 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (1.20), 0.008 (1.12), 3.036 L1): (16.00), 3.287(1.15), 4.256 (0.82), 4.265 Rt = 1.28 (0.81), 6.785 (0.91), 6.788(1.01), 6.805 min; MS (1.04), 6.808 (1.09), 6.923 (0.98), 6.926(ESIpos): (0.95), 6.942 (0.61), 7.171 (0.77), 7.355 m/z = 510 (0.79),7.374 (0.75), 7.674 (1.45), 7.677 [M + H]+ (3.02), 7.681 (6.87), 7.684(2.17), 7.687 (1.35), 7.794 (0.76), 7.801 (1.01), 7.816 (0.76), 7.823(0.93), 7.884 (0.86), 7.892 (0.85), 7.910 (0.84), 7.917 (0.75), 8.627(3.52), 9.120 (0.88), 9.140 (0.86). 41 LC-MS ¹H-NMR (400 MHz, DMSO-d6)delta (Method [ppm]: 3.035 (16.00), 3.287 (1.06), 4.256 L1): (0.95),4.266 (0.97), 6.788 (1.08), 6.808 Rt = 1.29 (1.19), 6.924 (1.08), 7.173(0.90), 7.355 min; MS (0.95), 7.374 (0.86), 7.810 (0.67), 7.817(ESIpos): (0.87), 7.833 (0.70), 7.840 (0.82), 7.861 m/z = 528 (3.09),7.878 (3.15), 7.884 (0.99), 7.891 [M + H]+ (0.79), 7.910 (0.83), 7.917(0.71), 8.631 (3.37), 9.121 (1.00), 9.142 (0.97). 42 LC-MS ¹H-NMR (400MHz, DMSO-d6) delta (Method [ppm]: 2.084 (0.98), 2.091 (0.83), 2.207L1): (0.87), 2.219 (0.85), 2.229 (0.81), 3.239 Rt = 1.31 (2.45), 3.250(5.46), 3.261 (5.61), 3.272 min; MS (2.65), 3.288 (1.94), 3.860 (4.44),3.872 (ESIpos): (7.25), 3.883 (4.20), 4.238 (1.42), 4.245 m/z = 552(1.11), 4.259 (1.49), 4.266 (1.84), 4.275 [M + H]+ (1.47), 4.281 (1.19),4.290 (1.20), 5.250 (1.36), 5.269 (1.34), 6.787 (2.49), 6.807 (2.79),6.913 (1.30), 6.916 (0.97), 6.932 (2.70), 6.950 (1.60), 7.154 (1.30),7.175 (2.09), 7.193 (1.03), 7.377 (2.28), 7.395 (2.06), 7.684 (12.45),7.686 (16.00), 7.839 (1.47), 7.843 (1.61), 7.846 (1.80), 7.861 (1.53),7.869 (1.65), 7.892 (1.84), 7.899 (1.55), 7.917 (1.79), 7.924 (1.38),8.694 (6.98), 9.201 (2.39), 9.221 (2.33). 43 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: −0.149 (0.62), −0.008 (6.95), L1): 0.008(6.61), 0.146 (0.77), 1.146 (1.05), Rt = 1.31 1.235 (0.81), 2.085(1.58), 2.208 (1.53), min; MS 2.327 (0.77), 2.366 (1.29), 2.670 (0.91),(ESIpos): 2.709 (1.39), 3.249 (9.34), 3.260 (9.68), m/z = 570 3.287(9.96), 3.861 (7.43), 3.872 (12.12), [M + H]+ 3.883 (7.23), 4.238(2.40), 4.266 (3.02), 4.275 (2.49), 4.292 (2.01), 5.250 (2.25), 5.269(2.25), 6.790 (4.07), 6.808 (4.50), 6.916 (2.01), 6.932 (4.26), 6.954(2.49), 7.159 (2.20), 7.176 (3.50), 7.197 (1.72), 7.377 (3.69), 7.396(3.50), 7.856 (2.83), 7.863 (5.37), 7.868 (13.51), 7.884 (16.00), 7.891(4.55), 7.898 (2.97), 7.916 (3.26), 7.923 (2.54), 8.700 (13.03), 9.202(3.83), 9.222 (3.78). 44 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method[ppm]: −0.008 (2.21), 0.008 (2.14), 2.301 L1): (2.93), 2.377 (7.46),3.062 (16.00), 4.263 Rt = 0.90 (0.86), 4.270 (0.99), 6.785 (1.06), 6.788min; MS (1.15), 6.805 (1.22), 6.808 (1.26), 6.905 (ESIpos): (0.56),6.908 (0.59), 6.924 (1.13), 6.927 m/z = 472 (1.11), 6.943 (0.70), 6.946(0.67), 7.153 [M + H]+ (0.60), 7.170 (0.91), 7.286 (1.86), 7.333 (1.69),7.335 (1.73), 7.358 (0.93), 7.374 (0.87), 7.417 (1.07), 7.421 (1.60),7.610 (0.86), 7.627 (1.27), 7.631 (1.03), 7.648 (1.23), 7.712 (1.31),7.716 (1.44), 7.730 (0.99), 7.734 (0.91), 8.169 (2.71), 8.193 (1.12),8.196 (1.15), 8.214 (1.07), 8.218 (1.00), 8.609 (4.09), 9.077 (0.98),9.098 (0.96). 45 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.008 (2.87), 0.008 (2.38), 3.066 L1): (16.00), 4.242 (0.72), 4.261(1.05), 4.269 Rt = 0.89 (1.17), 6.785 (1.14), 6.788 (1.20), 6.805 min;MS (1.30), 6.808 (1.32), 6.906 (0.63), 6.909 (ESIpos): (0.64), 6.924(1.28), 6.928 (1.24), 6.943 m/z = 476 (0.82), 6.946 (0.75), 7.149(0.62), 7.153 [M + H]+ (0.66), 7.171 (1.01), 7.352 (0.99), 7.371 (1.02),7.477 (0.90), 7.498 (1.55), 7.521 (1.34), 7.580 (0.77), 7.586 (0.81),7.593 (0.84), 7.598 (0.88), 7.602 (0.64), 7.607 (0.63), 7.614 (0.57),7.622 (1.17), 7.639 (1.40), 7.643 (1.20), 7.661 (1.36), 7.754 (1.52),7.758 (1.56), 7.772 (1.24), 7.776 (1.13), 7.788 (1.17), 7.794 (1.08),7.807 (1.15), 7.812 (1.07), 8.205 (1.23), 8.208 (1.27), 8.226 (1.17),8.230 (1.10), 8.278 (0.69), 8.614 (3.82), 9.077 (1.08), 9.098 (1.06). 46LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.149 (0.83),−0.008 (7.27), L1): 0.008 (6.79), 0.146 (0.83), 2.033 (0.69), Rt = 0.942.041 (0.72), 2.053 (0.69), 2.068 (1.10), min; MS 2.076 (0.89), 2.083(0.66), 2.176 (0.69), (ESIpos): 2.189 (0.92), 2.201 (0.92), 2.211(0.83), m/z = 476 2.236 (0.60), 2.366 (0.98), 2.710 (1.04), [M + H]+3.074 (16.00), 4.241 (1.55), 4.249 (1.37), 4.261 (2.38), 4.269 (2.62),4.285 (1.40), 5.226 (0.60), 5.241 (1.40), 5.260 (1.40), 5.275 (0.63),6.785 (2.53), 6.788 (2.68), 6.806 (2.92), 6.809 (2.95), 6.906 (1.43),6.909 (1.46), 6.924 (2.86), 6.928 (2.74), 6.943 (1.82), 6.946 (1.67),7.150 (1.52), 7.154 (1.49), 7.171 (2.23), 7.189 (1.16), 7.193 (1.13),7.356 (2.32), 7.374 (2.20), 7.429 (1.13), 7.432 (1.46), 7.435 (2.47),7.438 (2.26), 7.446 (1.31), 7.453 (2.06), 7.457 (2.41), 7.459 (2.77),7.463 (2.86), 7.468 (1.43), 7.473 (1.61), 7.478 (1.13), 7.515 (3.04),7.519 (4.35), 7.523 (2.26), 7.625 (0.72), 7.631 (2.68), 7.649 (2.86),7.652 (2.59), 7.670 (2.77), 7.790 (2.95), 7.794 (3.10), 7.809 (2.47),7.812 (2.32), 8.232 (2.15), 8.235 (2.18), 8.253 (2.06), 8.256 (1.97),8.418 (1.28), 8.623 (3.81), 9.088 (2.12), 9.108 (2.06). 47 LC-MS ¹H-NMR(400 MHz, DMSO-d6) delta (Method [ppm]: −0.149 (0.98), −0.011 (6.35),L1): −0.008 (14.61), 0.008 (8.04), 0.146 Rt = 0.92 (1.09), 1.147 (0.63),2.033 (1.06), 2.041 min; MS (1.06), 2.052 (1.09), 2.068 (1.50), 2.075(ESIpos): (1.28), 2.083 (0.90), 2.176 (1.09), 2.189 m/z = 478 (1.39),2.201 (1.31), 2.211 (1.20), 2.669 [M + H]+ (0.60), 3.079 (16.00), 4.220(0.82), 4.240 (2.37), 4.249 (2.02), 4.260 (3.57), 4.269 (3.60), 4.275(2.15), 4.285 (1.88), 4.304 (0.65), 5.228 (0.95), 5.240 (1.99), 5.261(1.91), 5.275 (0.82), 6.787 (3.71), 6.790 (3.68), 6.807 (4.17), 6.810(3.93), 6.906 (2.15), 6.909 (2.07), 6.924 (4.01), 6.928 (3.68), 6.943(2.53), 6.947 (2.18), 7.152 (2.07), 7.156 (2.10), 7.173 (3.11), 7.190(1.58), 7.194 (1.53), 7.352 (3.08), 7.371 (3.03), 7.558 (4.31), 7.575(4.63), 7.581 (5.34), 7.599 (4.61), 7.608 (0.93), 7.632 (2.81), 7.650(3.84), 7.653 (3.35), 7.671 (3.43), 7.791 (4.03), 7.795 (4.09), 7.809(3.35), 7.813 (2.94), 8.233 (2.78), 8.254 (2.40), 8.444 (1.55), 8.617(4.03), 9.093 (2.64), 9.113 (2.53). 48 LC-MS ¹H-NMR (400 MHz, DMSO-d6)delta (Method [ppm]: −0.149 (1.64), −0.008 (16.00), L1): 0.008 (12.95),0.146 (1.58), 1.147 (1.58), Rt = 0.98 2.025 (1.87), 2.033 (2.09), 2.045(2.32), min; MS 2.060 (3.17), 2.068 (2.71), 2.169 (2.04), (ESIpos):2.181 (2.94), 2.195 (2.83), 2.203 (2.83), m/z = 526 2.217 (1.87), 2.327(1.02), 2.366 (2.15), [M + H]+ 2.669 (1.30), 2.709 (2.20), 3.193 (6.61),4.195 (1.58), 4.216 (4.24), 4.237 (3.56), 4.253 (3.34), 4.262 (4.35),4.269 (3.79), 4.278 (3.96), 4.289 (1.70), 4.297 (1.92), 5.198 (1.70),5.212 (3.84), 5.232 (3.84), 6.786 (7.41), 6.789 (7.75), 6.807 (8.54),6.810 (8.59), 6.888 (4.13), 6.891 (4.18), 6.907 (8.65), 6.910 (8.37),6.925 (5.37), 6.928 (4.98), 7.149 (4.18), 7.153 (4.35), 7.171 (6.78),7.188 (3.34), 7.192 (3.39), 7.341 (7.24), 7.360 (6.90), 7.446 (3.39),7.466 (2.77), 7.516 (4.01), 7.681 (4.47), 7.699 (5.88), 7.720 (4.01),7.798 (2.94), 8.345 (2.37), 8.479 (3.11), 9.124 (3.00), 9.144 (3.05). 49LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.149 (1.77),−0.008 (16.00), L1): 0.008 (13.79), 0.146 (1.77), 1.147 (1.47), Rt =0.86 2.040 (1.77), 2.067 (2.73), 2.073 (2.21), min; MS 2.189 (2.43),2.201 (2.36), 2.211 (2.29), (ESIpos): 2.327 (1.40), 2.366 (2.73), 2.669(1.40), m/z = 460 2.710 (2.65), 3.179 (6.34), 4.207 (1.25), [M + H]+4.228 (3.47), 4.249 (3.02), 4.259 (3.32), 4.270 (3.61), 4.276 (3.02),4.286 (3.10), 4.304 (1.33), 5.225 (3.17), 5.245 (3.10), 6.420 (0.59),6.443 (0.59), 6.792 (6.34), 6.795 (6.64), 6.813 (7.37), 6.816 (7.30),6.900 (3.39), 6.903 (3.47), 6.918 (6.93), 6.922 (6.78), 6.937 (4.50),6.940 (4.35), 7.156 (3.54), 7.160 (3.61), 7.178 (5.46), 7.195 (3.24),7.199 (2.80), 7.217 (0.66), 7.241 (1.11), 7.265 (0.74), 7.319 (9.07),7.324 (9.73), 7.345 (12.90), 7.366 (6.05), 7.377 (1.84), 7.382 (1.92),7.398 (1.62), 7.404 (1.33), 7.653 (3.10), 7.671 (4.87), 7.692 (3.76),7.820 (4.87), 7.836 (3.98), 8.132 (1.25), 8.280 (2.36), 8.538 (1.62),9.132 (2.51). 50 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.149 (1.73), −0.008 (16.00), L1): 0.008 (14.73), 0.146 (1.80), 1.147(1.73), Rt = 0.96 2.033 (2.47), 2.045 (2.87), 2.060 (3.80), min; MS2.075 (2.47), 2.167 (2.47), 2.180 (3.53), (ESIpos): 2.192 (3.47), 2.201(3.33), 2.214 (2.40), m/z = 510 2.327 (1.33), 2.366 (2.40), 2.669(1.53), [M + H]+ 2.710 (2.40), 3.162 (9.07), 4.196 (1.80), 4.217 (5.20),4.238 (4.73), 4.250 (4.93), 4.260 (5.33), 4.267 (4.60), 4.275 (4.67),4.295 (2.07), 5.197 (2.00), 5.213 (4.67), 5.232 (4.67), 5.245 (2.20),6.784 (9.40), 6.786 (10.33), 6.804 (10.73), 6.807 (11.13), 6.887 (5.20),6.890 (5.40), 6.906 (10.73), 6.909 (10.67), 6.924 (6.47), 6.928 (6.20),7.147 (5.13), 7.151 (5.33), 7.168 (8.33), 7.185 (4.13), 7.189 (4.07),7.347 (8.87), 7.363 (8.33), 7.540 (4.60), 7.680 (3.40), 7.698 (6.33),7.719 (4.87), 7.790 (8.33), 7.878 (3.47), 8.132 (1.13), 8.342 (3.00),8.498 (4.40), 9.120 (3.87), 9.138 (3.87). 51 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: −0.149 (1.69), −0.008 (16.00), L1): 0.008(14.14), 0.146 (1.86), 1.147 (1.52), Rt = 0.89 2.032 (1.78), 2.060(2.62), 2.183 (2.37), min; MS 2.196 (2.29), 2.205 (2.20), 2.218 (1.61),(ESIpos): 2.328 (1.27), 2.332 (1.02), 2.366 (2.88), m/z = 476 2.670(1.44), 2.710 (3.05), 3.203 (4.99), [M + H]+ 4.196 (1.27), 4.217 (3.30),4.237 (2.88), 4.263 (3.56), 4.271 (3.05), 4.280 (3.13), 5.211 (3.13),5.231 (3.13), 6.787 (6.26), 6.790 (6.52), 6.808 (7.20), 6.811 (7.11),6.889 (3.64), 6.892 (3.64), 6.908 (7.53), 6.911 (6.94), 6.927 (4.49),6.930 (4.23), 7.151 (3.56), 7.155 (3.56), 7.172 (5.59), 7.189 (2.79),7.193 (2.96), 7.346 (7.28), 7.364 (8.30), 7.436 (3.30), 7.697 (5.67),7.718 (4.06), 7.778 (2.46), 8.132 (1.69), 8.336 (1.86), 8.478 (2.12),9.127 (2.37). 52 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]:−0.150 (0.80), −0.008 (7.08), L6): 0.008 (6.23), 0.146 (0.85), 1.147(0.94), Rt = 2.17 1.234 (1.04), 1.401 (0.66), 2.061 (1.98), min; MS2.184 (1.46), 2.196 (1.94), 2.208 (1.84), (ESIpos): 2.218 (1.84), 2.327(0.66), 2.366 (1.32), m/z = 534 2.669 (0.76), 2.710 (1.37), 3.288(16.00), [M + H]+ 3.336 (2.41), 3.866 (9.35), 3.876 (15.01), 3.888(8.54), 4.211 (1.09), 4.231 (3.26), 4.239 (2.55), 4.252 (4.48), 4.262(4.25), 4.270 (2.78), 4.279 (2.83), 4.298 (0.94), 5.241 (2.45), 5.256(2.41), 5.754 (5.00), 6.777 (5.57), 6.794 (5.95), 6.797 (6.14), 6.893(2.17), 6.912 (4.63), 6.930 (2.69), 7.140 (2.64), 7.161 (4.58), 7.178(2.08), 7.304 (1.84), 7.307 (1.98), 7.323 (2.88), 7.327 (3.59), 7.333(2.45), 7.352 (7.69), 7.370 (4.44), 7.413 (2.17), 7.424 (2.55), 7.432(3.73), 7.444 (4.11), 7.451 (2.08), 7.463 (2.03), 7.655 (2.12), 7.659(2.93), 7.672 (7.74), 7.677 (7.17), 7.684 (14.35), 7.687 (8.73), 7.704(12.93), 7.707 (7.46), 7.722 (3.26), 8.277 (5.38), 8.282 (5.47), 8.297(4.91), 8.302 (4.67), 8.583 (8.50), 8.590 (9.39), 9.143 (2.27), 9.158(3.16), 9.178 (2.55). 53 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method[ppm]: −0.011 (3.43), −0.008 (7.74), L1): 0.008 (4.34), 0.146 (0.57),1.157 (2.48), Rt = 1.02 1.175 (4.93), 1.193 (2.43), 1.988 (8.75), min;MS 2.057 (0.67), 2.072 (0.90), 2.080 (0.75), (ESIpos): 2.204 (0.82),2.216 (0.77), 2.225 (0.77), m/z = 532 3.272 (2.97), 3.285 (6.13), 3.297(8.04), [M + H]+ 3.863 (4.09), 3.875 (6.63), 3.887 (3.55), 3.945(16.00), 4.003 (0.72), 4.021 (2.03), 4.038 (2.03), 4.056 (0.67), 4.236(1.36), 4.244 (1.09), 4.257 (1.56), 4.270 (1.44), 4.277 (1.09), 4.286(1.09), 5.250 (1.24), 5.269 (1.16), 6.780 (2.31), 6.783 (2.38), 6.800(2.55), 6.803 (2.50), 6.902 (1.27), 6.906 (1.27), 6.921 (2.43), 6.924(2.23), 6.940 (1.54), 6.943 (1.36), 7.100 (0.70), 7.115 (1.01), 7.121(1.41), 7.128 (0.80), 7.137 (1.63), 7.140 (1.61), 7.146 (1.99), 7.151(1.98), 7.156 (1.37), 7.166 (2.21), 7.168 (2.40), 7.186 (1.12), 7.190(1.14), 7.195 (1.44), 7.199 (1.34), 7.216 (1.04), 7.221 (2.01), 7.226(1.29), 7.243 (0.85), 7.247 (0.80), 7.353 (0.64), 7.356 (0.82), 7.361(2.01), 7.374 (1.09), 7.377 (1.11), 7.381 (1.86), 7.391 (0.57), 7.465(0.90), 7.485 (0.60), 7.676 (1.27), 7.694 (3.10), 7.714 (4.29), 7.717(3.84), 7.722 (3.60), 7.734 (1.24), 7.739 (0.70), 8.095 (0.60), 8.278(2.26), 8.283 (2.09), 8.298 (2.13), 8.303 (1.81), 8.615 (10.00), 9.154(2.23), 9.175 (2.11). 54 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method[ppm]: −0.149 (1.29), −0.008 (12.61), L1): 0.008 (10.72), 0.146 (1.29),1.147 (0.91), Rt = 1.24 1.235 (0.73), 1.988 (0.80), 2.087 (1.68), min;MS 2.210 (1.47), 2.231 (1.33), 2.366 (1.33), (ESIpos): 2.710 (1.40),3.267 (4.16), 3.278 (9.96), m/z = 552 3.287 (15.97), 3.864 (7.30), 3.876[M + H]+ (12.16), 3.888 (7.06), 4.224 (0.73), 4.244 (2.38), 4.252(1.92), 4.265 (3.14), 4.276 (3.00), 4.292 (2.06), 5.255 (2.20), 5.275(2.24), 6.789 (4.37), 6.810 (4.72), 6.916 (1.99), 6.919 (2.06), 6.934(4.26), 6.953 (2.59), 7.154 (2.24), 7.158 (2.17), 7.175 (3.49), 7.192(1.71), 7.381 (3.70), 7.399 (3.42), 7.681 (3.00), 7.699 (4.19), 7.702(3.95), 7.720 (3.84), 7.806 (14.46), 7.822 (14.43), 7.843 (4.61), 7.846(4.93), 7.861 (3.77), 7.864 (3.67), 8.273 (3.95), 8.277 (4.12), 8.295(3.81), 8.298 (3.67), 8.704 (16.00), 9.165 (3.98), 9.186 (3.91). 55LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (1.58),0.008 (1.48), L6): 3.056 (16.00), 3.065 (1.61), 3.289 (1.47), Rt = 1.443.903 (10.43), 3.909 (1.22), 4.271 (0.85), min; MS 6.785 (0.92), 6.788(1.00), 6.805 (1.06), (ESIpos): 6.808 (1.08), 6.926 (1.03), 6.929(0.97), m/z = 472 6.945 (0.63), 7.171 (0.82), 7.220 (0.62), [M + H]+7.242 (1.22), 7.264 (0.82), 7.354 (0.82), 7.374 (1.35), 7.376 (1.39),7.382 (0.75), 7.475 (0.94), 7.480 (0.83), 7.507 (0.90), 7.513 (0.86),7.597 (0.76), 7.615 (1.05), 7.618 (0.89), 7.636 (1.04), 7.717 (1.17),7.721 (1.25), 7.735 (0.90), 7.739 (0.84), 8.156 (1.01), 8.160 (1.04),8.177 (0.96), 8.181 (0.89), 8.608 (4.20), 9.075 (0.90), 9.096 (0.86). 56LC-MS ¹H-NMR (500 MHz, DMSO-d6) delta (Method [ppm]: 2.403 (6.76), 3.060(16.00), 3.164 L6): (0.79), 3.174 (0.80), 4.261 (0.74), 6.787 Rt = 1.79(0.91), 6.789 (0.97), 6.803 (1.01), 6.806 min; MS (1.01), 6.925 (0.96),6.927 (0.92), 6.940 (ESIpos): (0.58), 7.170 (0.76), 7.355 (0.76), 7.370m/z = 472 (0.74), 7.431 (1.71), 7.447 (1.38), 7.451 [M + H]+ (1.32),7.614 (0.78), 7.629 (1.13), 7.631 (1.04), 7.636 (1.77), 7.639 (1.64),7.646 (1.03), 7.721 (1.15), 7.724 (1.19), 7.735 (0.90), 7.738 (0.83),8.185 (1.00), 8.188 (1.01), 8.202 (0.95), 8.205 (0.87), 8.601 (3.95),9.077 (0.87), 9.094 (0.83). 57 LC-MS ¹H-NMR (500 MHz, DMSO-d6) delta(Method [ppm]: 3.070 (16.00), 6.781 (0.93), 6.783 L1): (1.06), 6.797(1.06), 6.799 (1.13), 6.915 Rt = 0.92 (0.96), 6.917 (1.03), 6.932(0.60), 7.165 min; MS (0.83), 7.344 (0.86), 7.358 (0.80), 7.637(ESIpos): (0.80), 7.652 (1.06), 7.654 (0.90), 7.669 m/z = 478 (1.03),7.716 (1.03), 7.718 (1.16), 7.730 [M + H]+ (0.77), 7.732 (0.77), 8.251(0.96), 8.254 (1.06), 8.268 (0.93), 8.271 (0.93), 8.559 (3.79), 9.074(0.90), 9.090 (0.86). 58 2.11 ¹H-NMR (399, 9532 MHz, DMSO) δ = 8.8706(0.51), 8.8451 (2.08), 8.4185 (0.68), 8.4155 (0.7), 8.3974 (0.66),8.3942 (0.64), 8.3138 (0.34), 7.7984 (0.62), 7.7955 (0.67), 7.7805(0.77), 7.7776 (0.75), 7.664 (3.27), 7.6592 (3.77), 7.602 (0.98), 7.5971(1.58), 7.5922 (0.8), 7.5884 (0.66), 7.5699 (0.62), 7.5674 (0.69),7.5491 (0.53), 7.2426 (0.53), 7.2249 (0.57), 7.1558 (0.53), 7.1387(0.34), 6.8988 (0.39), 6.896 (0.43), 6.8801 (0.66), 6.8773 (0.7), 6.8616(0.34), 6.8587 (0.35), 6.806 (0.78), 6.8035 (0.77), 6.7857 (0.73),6.7829 (0.66), 5.3292 (0.33), 4.3233 (0.33), 4.2445 (0.35), 3.315(36.45), 2.6749 (0.48), 2.6702 (0.67), 2.6656 (0.48), 2.5236 (1.77),2.5187 (2.78), 2.5102 (37.2), 2.5056 (77.48), 2.501 (107.64), 2.4965(79.14), 2.492 (37.03), 2.3325 (0.44), 2.3279 (0.63), 2.3234 (0.47),1.9882 (0.43), 1.398 (16), 0.008 (1.74), −0.0001 (52.5), −0.0085 (1.57)59 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (3.35),0.008 (3.16), L1): 2.093 (0.79), 2.366 (0.71), 2.710 (0.67), Rt = 1.422.925 (16.00), 3.287 (2.93), 4.247 (1.14), min; MS 4.254 (1.00), 4.266(1.71), 4.274 (1.91), (ESIpos): 4.289 (1.02), 4.422 (6.70), 5.298(1.04), m/z = 568 5.319 (1.04), 6.784 (2.02), 6.787 (2.18), [M + H]+6.804 (2.31), 6.807 (2.37), 6.889 (1.10), 6.893 (1.06), 6.908 (2.16),6.911 (2.08), 6.927 (1.37), 6.930 (1.31), 7.145 (1.10), 7.150 (1.10),7.167 (1.66), 7.184 (0.83), 7.188 (0.85), 7.302 (0.69), 7.319 (1.89),7.333 (0.81), 7.337 (1.46), 7.341 (0.81), 7.389 (2.00), 7.405 (3.56),7.408 (5.68), 7.421 (2.41), 7.427 (4.85), 7.444 (4.93). 7.461 (2.10),7.465 (1.46), 7.642 (1.14), 7.646 (2.04), 7.647 (2.98), 7.651 (5.53),7.656 (14.31), 7.660 (4.91), 7.690 (1.73), 7.708 (2.27), 7.711 (1.98),7.729 (2.16), 7.835 (2.54), 7.838 (2.66), 7.853 (2.02), 7.857 (1.91).8.318 (2.18), 8.321 (2.23), 8.339 (2.06), 8.343 (1.85), 8.752 (9.09),9.153 (2.02), 9.174 (1.98). 60 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.988 (0.48), 2.044 (0.43), 2.085 (0.43), L1): 3.066 (2.26),3.075 (16.00), 3.169 (2.25), Rt = 0.85 4.230 (0.60), 4.249 (0.92), 4.257(1.04), min; MS 4.271 (0.62), 5.227 (0.50), 5.244 (0.54), (ESIpos):6.775 (1.07), 6.793 (1.18), 6.884 (0.51), m/z = 476 6.903 (1.06), 6.922(0.68), 7.141 (0.56), [M + H]+ 7.158 (0.91), 7.175 (0.50), 7.214 (0.55),7.331 (0.84), 7.351 (0.82), 7.438 (1.23), 7.449 (1.52), 7.460 (1.03),7.467 (1.28), 7.625 (0.51), 7.638 (2.53), 7.642 (1.75), 7.657 (1.45),7.674 (0.45), 8.228 (0.46), 8.248 (0.96), 8.254 (0.96), 8.266 (0.84),8.273 (0.82), 8.522 (3.66), 9.072 (0.54), 9.091 (0.52). 61 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (4.15), 0.008 (3.77), 2.366(1.07), L6): 2.386 (6.43), 2.710 (1.00), 3.060 (16.00), Rt = 1.62 3.287(5.91), 3.681 (0.59), 4.270 (0.79), min; MS 6.787 (0.97), 6.805 (1.00),6.808 (1.04), (ESIpos): 6.923 (0.93), 6.942 (0.66), 7.187 (0.86), m/z =456 7.221 (1.56), 7.355 (0.76), 7.372 (0.76), [M + H]+ 7.608 (0.76),7.626 (1.07), 7.629 (0.93), 7.647 (1.04), 7.717 (1.14), 7.720 (1.21),7.734 (0.90), 7.738 (0.79), 8.188 (1.00), 8.192 (1.04), 8.210 (0.93),8.214 (0.90), 8.606 (3.97), 9.077 (0.83). 9.097 (0.79). 62 LC-MS ¹H-NMR(500 MHz, (Method DICHLOROMETHANE-d2) δ [ppm]: L6): 3.078 (16.00), 4.203(0.84), 5.308 (0.97), Rt = 1.27 5.320 (1.31), 5.341 (0.74), 5.356(0.72), min; MS 6.815 (1.16), 6.831 (1.27), 6.913 (1.20), (ESIpos):6.927 (0.69), 7.165 (0.71), 7.179 (1.10), m/z = 443 7.297 (0.77), 7.305(0.99), 7.315 (1.75), [M + H]+ 7.331 (1.10), 7.446 (0.67), 7.463 (1.09),7.554 (0.91), 7.569 (1.18), 7.571 (1.18), 7.586 (0.87), 7.726 (1.17),7.728 (1.20), 7.740 (1.02), 7.741 (1.01), 8.152 (1.65), 8.166 (1.87),8.673 (2.52). 63 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 2.362(0.64), 2.635 (0.64), 3.075 (16.00), L6): 6.787 (0.94), 6.790 (1.04),6.804 (1.04), Rt = 1.57 6.806 (1.09), 6.925 (0.94), 6.927 (0.99), min;MS 6.942 (0.59), 7.171 (0.79), 7.355 (0.84), (ESIpos): 7.369 (0.79),7.422 (1.78), 7.603 (0.74), m/z = 443 7.612 (0.79), 7.670 (0.79), 7.684(0.99), [M + H]+ 7.687 (0.99), 7.702 (0.89), 7.857 (1.04), 7.859 (1.19),7.871 (0.99), 7.873 (1.04), 8.279 (0.99), 8.282 (1.09), 8.296 (0.99),8.301 (1.88), 8.311 (1.39), 8.626 (3.76), 9.094 (0.84), 9.110 (0.84). 64LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (1.17), 3.065(16.00), 3.909 L6): (9.18), 4.260 (0.93), 4.268 (0.99), 5.752 Rt = 1.48(2.29), 6.786 (1.02), 6.803 (1.15), 6.806 min; MS (1.15), 6.923 (1.06),6.941 (0.64), 7.014 (ESIpos): (1.90), 7.016 (2.04), 7.169 (0.88), 7.194m/z = 455 (1.22), 7.197 (1.12), 7.207 (1.15), 7.210 [M + H]+ (1.10),7.349 (0.91), 7.368 (0.83), 7.632 (0.74), 7.650 (1.07), 7.653 (0.90),7.671 (0.98), 7.768 (1.17), 7.772 (1.15), 7.785 (0.90), 7.789 (0.83),8.205 (1.69), 8.218 (1.63), 8.232 (1.04), 8.236 (1.05), 8.254 (0.98),8.257 (0.90), 8.602 (3.69), 9.076 (0.93), 9.097 (0.90). 65 LC-MS ¹H-NMR(500 MHz, DMSO-d6) δ [ppm]: (Method 2.362 (0.80), 2.635 (0.74), 3.074(16.00), L6): 4.264 (0.74), 6.790 (1.04), 6.804 (1.04), Rt = 1.69 6.806(1.16), 6.926 (0.98), 6.928 (1.04), min; MS 6.941 (0.55), 7.173 (0.80),7.358 (0.86), (ESIpos): 7.372 (0.80), 7.654 (1.04), 7.657 (1.16), m/z =459 7.667 (1.66), 7.680 (0.98), 7.683 (0.98), [M + H]+ 7.697 (0.92),7.752 (1.90), 7.753 (1.96), 7.849 (1.04), 7.852 (1.16), 7.864 (0.98),7.866 (0.98), 8.277 (0.98), 8.280 (1.10), 8.294 (0.92), 8.297 (0.98),8.479 (1.53), 8.489 (1.53), 8.630 (3.74), 9.093 (0.92), 9.109 (0.92). 66LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method −0.007 (3.16), 0.007(2.43), 2.085 (0.91), L6): 2.479 (16.00), 3.063 (15.53), 3.290 Rt = 1.08(1.71), 4.259 (0.73), 5.753 (4.07), 6.787 min; MS (0.96), 6.789 (1.08),6.805 (1.15), 6.923 (ESIpos): (1.01), 6.925 (1.05), 6.938 (0.58), 6.940m/z = 453 (0.59), 7.170 (0.86), 7.229 (4.94), 7.355 [M + H]+ (0.90),7.369 (0.82), 7.626 (0.70), 7.640 (1.04), 7.643 (0.94), 7.657 (0.96),7.718 (1.11), 7.721 (1.23), 7.732 (0.83), 7.735 (0.84), 8.141 (0.84),8.219 (0.97), 8.222 (1.05), 8.236 (0.90), 8.239 (0.91), 8.601 (3.53),9.079 (0.94), 9.095 (0.92). 67 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (1.73), 0.008 (1.62), 1.083 (7.08), L1): 1.101 (16.00),1.119 (7.35), 2.523 (1.15), Rt = 1.42 3.360 (2.01), 3.378 (5.98), 3.395(5.74), min; MS 3.413 (1.81), 4.238 (1.03), 4.246 (0.84), (ESIpos):4.259 (1.48), 4.269 (1.39), 4.277 (0.92), m/z = 520 4.286 (0.88), 5.239(0.96), 5.259 (0.94), [M + H]+ 6.786 (1.61), 6.789 (1.77), 6.807 (1.84),6.809 (1.93), 6.913 (0.87), 6.916 (0.88), 6.931 (1.76), 6.934 (1.80),6.950 (1.09), 6.953 (1.08), 7.152 (0.90), 7.156 (0.98), 7.174 (1.49),7.191 (0.74), 7.195 (0.72), 7.362 (1.54), 7.378 (1.43), 7.628 (0.85),7.634 (2.10), 7.638 (4.21), 7.644 (9.24), 7.649 (4.32), 7.657 (2.01),7.660 (1.75), 7.678 (1.75), 7.797 (1.98), 7.800 (2.12), 7.815 68 LC-MS¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 1.845 (0.84), 2.040 (0.83),2.050 (0.89), L1): 2.057 (0.88), 2.068 (0.71), 4.052 (0.72), Rt = 1.364.064 (0.80), 4.069 (1.50), 4.075 (0.94), min; MS 4.087 (0.97). 4.092(0.74), 4.167 (0.77), (ESIpos): 4.172 (0.97), 4.180 (0.89), 4.187(1.11), m/z = 583 5.072 (1.29), 5.088 (1.26), 5.753 (0.58), [M + H]+6.752 (2.43), 6.754 (2.55), 6.768 (2.63), 6.771 (2.67), 6.844 (1.23),6.846 (1.20), 6.859 (2.46), 6.861 (2.43), 6.874 (1.49), 6.876 (1.41),7.069 (2.20), 7.082 (1.84), 7.134 (1.29), 7.138 (1.18), 7.151 (2.04),7.165 (1.14), 7.168 (0.92), 7.593 (2.44), 7.595 (2.47), 7.610 (2.69),7.612 (2.56), 7.680 (0.95), 7.709 (1.44), 7.711 (2.27), 7.713 (4.04),7.716 (8.15), 7.718 (16.00), 7.721 (5.44), 7.831 (2.20), 7.845 (2.64),7.848 (2.23), 7.863 (2.06), 8.037 (2.79), 8.039 (2.83), 8.051 (2.40),8.054 (2.29), 8.418 (6.05), 8.870 (4.59), 8.961 (0.63), 9.079 (2.41),9.095 (2.29), 9.192 (9.46). 69 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (4.56), 0.008 (2.59), L1): 1.234 (0.95), 1.880(1.58), 1.890 (0.87), Rt = 0.86 1.901 (1.75), 1.912 (1.84), 1.923(0.87), min; MS 1.933 (1.74), 2.350 (0.80), 2.361 (1.45), (ESIpos):2.369 (1.79), 2.381 (1.55), 2.392 (1.49), m/z = 514 2.401 (1.25), 2.775(0.78), 2.797 (1.46), [M + H]+ 2.816 (1.81), 2.837 (2.31), 2.858 (1.06),2.937 (1.44), 2.945 (1.55), 2.959 (1.61), 2.966 (1.48), 2.976 (1.06),2.985 (0.97), 2.998 (0.95), 3.005 (0.79), 5.345 (0.97), 5.365 (2.65),5.384 (2.58), 5.405 (0.85), 5.754 (15.35), 7.164 (0.99), 7.182 (3.03),7.195 (4.52), 7.200 (5.02), 7.215 (3.94), 7.230 (2.07), 7.247 (4.63),7.264 (2.46), 7.277 (3.90), 7.293 (2.68), 7.402 (2.41), 7.420 (3.40),7.441 (2.65), 7.539 (4.31), 7.610 (2.91), 7.615 (5.39), 7.620 (4.00),7.646 (16.00), 7.651 (11.73), 7.738 (4.35), 7.756 (3.85), 8.133 (12.50),8.155 (3.28), 8.795 (9.42), 8.838 (3.65), 8.858 (3.47), 9.979 (4.48),12.732 (2.72). 70 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 2.912(16.00), 3.056 (8.85), 3.304 (1.27), L6): 5.751 (0.73), 6.786 (0.85),6.788 (0.88), Rt = 1.42 6.802 (0.93), 6.805 (0.92), 6.832 (0.77), min;MS 6.848 (0.83), 6.883 (0.92), 6.887 (1.01), (ESIneg): 6.888 (1.00),6.921 (0.87), 6.923 (0.83), m/z = 465 7.219 (0.72), 7.235 (1.00), 7.251(0.60), [M − H]− 7.591 (0.61), 7.605 (0.91), 7.608 (0.71), 7.622 (0.84),7.675 (0.96), 7.678 (0.97), 7.689 (0.69), 8.132 (0.85), 8.150 (0.79),8.153 (0.78), 8.168 (0.74), 8.567 (2.33), 9.079 (0.74). 71 LC-MS ¹H-NMR(500 MHz, CHLOROFORM-d) (Method δ [ppm]: 3.144 (16.00), 3.851 (8.34),L6): 4.212 (0.71), 6.859 (1.08), 6.861 (1.16), Rt = 0.97 6.875 (1.18),6.877 (1.26), 6.908 (0.59), min; MS 6.910 (0.57), 6.923 (1.17), 6.925(1.11), (ESIneg): 6.938 (0.69), 6.940 (0.64), 7.204 (0.94), m/z = 4767.302 (0.98), 7.318 (0.92), 7.590 (0.88), [M − H]− 7.604 (1.17), 7.607(1.08). 7.621 (1.12), 7.653 (1.78), 7.757 (1.31), 7.760 (1.38), 7.772(1.15), 7.774 (1.07), 7.886 (0.77), 8.127 (1.09), 8.130 (1.10), 8.144(1.04), 8.147 (0.99), 9.040 (1.35). 72 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method 0.934 (0.65), 0.951 (1.40), 0.969 (0.72), L1): 1.815(0.91), 1.825 (1.04), 1.842 (1.24), Rt = 1.34 1.859 (0.77), 2.014(1.18), 2.027 (1.17), min; MS 2.035 (1.12), 2.049 (0.88), 2.694 (1.05),(ESIpos): 4.031 (0.92), 4.052 (1.96), 4.059 (1.36), m/z = 515 4.073(1.35), 4.080 (1.05), 4.158 (1.43), [M + H]+ 4.168 (1.30), 4.176 (1.62),4.186 (0.92), 4.196 (0.91), 5.044 (0.78), 5.058 (1.79), 5.077 (1.81),5.092 (0.82), 6.686 (3.38), 6.691 (5.17), 6.696 (3.37), 6.736 (3.20),6.754 (3.60), 6.845 (1.55), 6.864 (3.34), 6.883 (2.11), 7.082 (3.20),7.102 (2.64), 7.117 (1.82), 7.122 (1.57), 7.138 (2.83), 7.156 (1.43),7.665 (2.79), 7.668 (2.76), 7.686 (3.87), 7.689 (3.76), 7.710 (16.00),7.714 (7.25), 7.776 (2.70), 7.794 (3.62), 7.815 (2.25), 7.938 (5.43),7.942 (5.37), 7.987 (3.52), 7.990 (3.35), 8.005 (3.05), 8.008 (2.74),8.147 (5.19), 8.153 (5.21), 8.914 (3.01), 8.935 (2.93), 9.116 (10.01).73 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.06), 0.008(1.57), 2.133 (0.74), L1): 2.366 (0.70), 2.524 (2.87), 2.710 (0.70), Rt= 0.71 3.079 (16.00), 4.252 (0.87), 4.260 (0.94), min; MS 5.753 (3.02),5.955 (1.19), 6.777 (1.02), (ESIpos): 6.794 (1.11), 6.881 (0.59), 6.900(1.22), m/z = 463 6.902 (1.13), 6.918 (0.70), 7.029 (0.98), [M + H]+7.031 (1.06), 7.047 (1.44), 7.135 (1.44), 7.156 (2.13), 7.174 (1.26),7.248 (1.09), 7.254 (1.43), 7.262 (1.04), 7.308 (1.02), 7.322 (0.96),7.342 (0.81), 7.404 (1.37), 7.424 (1.15), 7.629 (0.83), 7.647 (1.07),7.650 (0.89), 7.668 (1.04), 7.733 (1.26), 7.737 (1.35), 7.751 (0.94),7.754 (0.87), 8.192 (1.00), 8.196 (1.04), 8.214 (0.98), 8.217 (0.87),8.469 (3.80), 9.059 (0.93), 9.080 (0.89), 11.099 (0.85). 74 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 3.169 (16.00), 3.645 (1.14), 3.658(1.38), L6): 6.782 (0.83), 6.799 (0.91), 6.803 (0.87), Rt = 1.42 6.899(0.86), 7.602 (1.31), 7.607 (1.19), min; MS 7.622 (4.81), 7.627 (2.96),8.133 (2.91), (ESIpos): 8.546 (2.19). m/z = 508 [M + H]+ 75 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (0.97), 0.008 (0.95), 2.085(1.49), L6): 3.061 (10.00), 3.173 (16.00), 3.455 Rt = 2.54 (2.24), 3.469(1.54), 3.554 (0.89), 3.567 min; MS (1.31), 3.585 (1.41), 6.788 (1.20),6.791 (ESIpos): (1.37), 6.809 (1.39), 6.812 (1.48), 6.926 m/z = 536(1.31), 6.929 (1.31), 6.944 (0.78), 6.947 [M + H]+ (0.77), 7.174 (1.05),7.357 (1.04), 7.372 (1.00), 7.637 (2.10), 7.641 (10.04), 7.645 (3.82),7.663 (1.38). 7.667 (1.27), 7.685 (1.30), 7.805 (1.45), 7.809 (1.59),7.823 (1.19), 7.827 (1.19), 8.299 (1.28), 8.303 (1.36), 8.320 (1.23),8.324 (1.19), 8.712 (5.32), 9.065 (1.22), 9.086 (1.19). 76 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.51), 0.008 (2.41), 2.063(1.06), L1): 2.073 (1.60), 2.143 (0.95), 2.157 (1.15), Rt = 0.92 2.327(0.87), 2.523 (2.45), 2.670 (0.84), min; MS 3.334 (4.14), 3.356 (4.85),3.567 (2.37), (ESIpos): 3.581 (5.84), 3.593 (3.89), 3.684 (3.13), m/z =522 3.697 (2.74), 4.269 (3.13), 4.278 (2.53), [M + H]+ 4.286 (1.74),5.247 (1.52), 5.266 (1.51), 6.783 (2.84), 6.786 (3.12), 6.804 (3.25),6.807 (3.39), 6.884 (1.49), 6.887 (1.55), 6.903 (3.11), 6.906 (3.03),6.921 (1.86), 6.924 (1.77), 7.143 (1.48), 7.148 (1.63), 7.165 (2.50),7.182 (1.18), 7.186 (1.20), 7.294 (2.53), 7.314 (2.37), 7.531 (1.18),7.551 (1.97), 7.569 (1.32), 7.609 (3.49), 7.614 (3.76), 7.624 (16.00),7.628 (9.17), 7.750 (2.78), 7.766 (2.37), 8.381 (1.85), 8.402 (1.76),8.558 (5.29), 9.023 (1.39), 9.042 (1.36). 77 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 2.063 (0.91), 3.712 (0.91), 4.023 (3.89), L1):4.028 (3.96), 4.242 (1.32), 4.251 (1.33), Rt = 0.88 4.261 (1.86), 4.270(2.06), 4.282 (1.19), min; MS 4.674 (1.12), 4.887 (1.03), 4.916 (1.04),(ESIpos): 4.929 (2.17), 4.947 (2.17), 4.961 (1.00), m/z = 533 5.241(1.16), 5.261 (1.09), 5.754 (5.20), [M + H]+ 6.794 (2.03), 6.814 (2.13),6.905 (0.96), 6.907 (1.01), 6.923 (1.92), 6.926 (1.96), 6.942 (1.13),6.945 (1.13), 7.156 (1.19), 7.160 (1.25), 7.177 (1.78), 7.195 (0.88),7.199 (0.81), 7.327 (1.71), 7.346 (1.58), 7.626 (1.09), 7.630 (1.31),7.640 (16.00), 7.647 (1.70), 7.659 (2.46), 7.664 (2.09), 7.681 (1.56),7.839 (1.82), 7.842 (2.20), 7.857 (1.59), 7.860 (1.81), 8.138 (2.43),8.305 (1.86), 8.309 (2.07), 8.327 (1.68), 8.330 (1.74), 8.711 (2.71),8.734 (6.72), 8.846 (0.69), 9.226 (1.85), 9.246 (1.78). 78 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 1.356 (0.92), 3.007 (16.00), 3.407(0.85), L1): 3.421 (1.08), 3.473 (1.23), 3.486 (0.97), Rt = 1.41 3.552(1.13), 3.559 (1.40), 3.565 (1.84), min; MS 3.573 (1.77), 5.754 (2.61),6.794 (0.83), (ESIpos): 6.813 (0.96), 6.927 (0.88), 7.329 (0.75), m/z =580 7.638 (0.93), 7.643 (1.08), 7.652 (3.47), [M + H]+ 7.657 (2.11),7.666 (0.89), 7.687 (0.67), 7.810 (0.96), 7.827 (0.77). 8.237 (0.79),8.240 (0.79), 8.258 (0.74), 8.764 (3.04), 8.881 (0.82), 8.901 (0.79). 79LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.20), 0.008(2.00), 1.091 (1.05), L6): 1.157 (1.00), 1.175 (2.17), 1.193 (1.28), Rt= 1.67 1.234 (2.13), 1.391 (1.14), 1.908 (3.71), min; MS 1.916 (4.42),1.924 (10.00), 1.932 (4.39), (ESIpos): 1.941 (3.75), 1.956 (1.50), 1.988(1.88), m/z = 502 2.462 (0.91), 2.472 (1.20), 2.689 (7.43), [M + H]+2.825 (0.94), 2.845 (1.20), 2.865 (1.56), 2.965 (0.92), 2.977 (0.96),3.288 (1.30), 3.650 (3.10), 3.666 (7.98), 3.682 (2.94), 5.489 (1.79).5.509 (1.80). 7.211 (2.58), 7.215 (2.00), 7.221 (3.24), 7.228 (2.98),7231 (3.71), 7.233 (3.97), 7.245 (1.09), 7.259 (2.43), 7.271 (1.46),7.356 (1.78), 7.365 (1.99), 7.377 (1.40), 7.477 (1.97), 7.495 (2.48),7.498 (2.33), 7.516 (2.30), 7.604 (1.42), 7.610 (3.39), 7.614 (5.27),7.620 (16.00), 7.624 (6.54), 7.709 (2.80), 7.713 (3.02), 7.727 (2.49),7.731 (2.42), 8.263 (2.41), 8.266 (2.49), 8.284 (2.32), 8288 (2.22),8.452 (9.01), 8.878 (2.24), 8.899 (2.20). 80 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.90), −0.008 (7.64), 0.008 L1):(7.69), 0.146 (0.95), 1.175 (0.44), 1.236 Rt = 0.91 (2.24), 1.879(1.70), 1.916 (1.03), 1.936 min; MS (0.98), 1.950 (0.87), 1.968 (0.77),1.988 (ESIpos): (0.87), 2.327 (1.36), 2.366 (1.49), 2.523 m/z = 546(5.17), 2.670 (1.57), 2.710 (1.16), 2.815 [M + H]+ (0.49), 2.835 (0.85),2.855 (1.11), 2.874 (1.26), 2.893 (0.67), 2.959 (0.72), 2.972 (0.87),2.981 (0.80), 2.993 (0.90), 3.021 (0.54), 3.798 (0.87), 3.816 (0.93),4.640 (1.05), 4.654 (1.23), 4.662 (1.13), 5.511 (0.54), 5.530 (1.39),5.549 (1.36), 5.567 (0.54), 7.231 (2.24), 7.240 (2.39), 7248 (3.68),7.253 (2.98), 7.271 (2.68), 7.285 (1.05), 7.446 (1.44), 7.453 (1.57),7.467 (1.34), 7.629 (1.65), 7.640 (16.00), 7.667 (1.67), 7.801 (2.32),7.816 (1.85), 8.282 (1.65), 8.301 (1.57), 8.695 (6.92), 12.590 (0.62).81 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (1.26), 0.008(1.50). 3.074 L1): (16.00), 4.253 (0.86), 4.262 (0.91), 5.754 Rt = 0.92(4.63), 6.778 (0.85), 6.781 (0.95), 6.799 min; MS (0.99), 6.801 (1.02),6.913 (0.95), 6.917 (ESIpos): (0.94), 6.932 (0.59), 7.164 (0.79), 7.343m/z = 478 (0.82), 7.648 (0.69), 7.665 (1.10), 7.669 [M + H]+ (0.79),7.687 (1.14), 7.721 (1.10), 7.725 (1.20), 7.739 (0.70), 7.743 (0.63),8.265 (0.99), 8.269 (1.00), 8.286 (0.94), 8.290 (0.86). 8.566 (3.67),9.075 (0.84). 9.096 (0.82). 82 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method[ppm]: 3.288 (1.60), 3.300 (2.14), 3.311 L6): (16.00), 3.865 (1.20),3.877 (2.00). 3.888 Rt = 2.08 (1.13), 6.780 (0.66), 6.783 (0.71), 6.800min; MS (0.74), 6.803 (0.77), 6.922 (0.70), 6.925 (ESIpos): (0.69),7.385 (0.70), 7.720 (0.80), 7.741 m/z = 520 (0.83), 7.764 (0.84), 7.768(0.91), 8.304 [M + H]+ (0.65), 8.308 (0.66), 8.325 (0.62), 8.635 (2.82),9.161 (0.64). 83 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(3.64), 0.008 (3.64), 1.988 (0.96), L6): 2.038 (0.93), 2.045 (0.98),2.057 (1.02), Rt = 2.26 2.073 (1.49). 2.080 (1.22). 2.189 (0.93), min;MS 2.203 (1.36), 2.215 (1.27), 2.224 (1.27), (ESIpos): 3.259 (1.29),3.277 (3.60), 3.290 (8.31), m/z = 568 3.334 (2.18). 3.610 (5.58), 3.867(6.16), [M + H]+ 3.880 (11.07), 3.892 (6.04), 4234 (2.20), 4.241 (1.69),4.254 (2.29), 4.261 (2.71), 4.269 (2.31), 4.275 (1.84), 4.285 (1.84).5.232 (0.89), 5.247 (2.02), 5.267 (2.02), 5281 (0.89), 6.685 (0.98),6.706 (1.07), 6.779 (3.53), 6.782 (3.93), 6.800 (4.02), 6.803 (4.29),6.901 (1.93), 6.904 (1.98), 6.919 (3.93), 6.922 (3.96), 6.938 (2.44),6.941 (2.38), 7.146 (1.98), 7.150 (2.13), 7.167 (3.18), 7.185 (1.62),7.189 (1.60), 7.363 (3.33), 7.380 (3.22), 7.384 (3.18), 7.389 (2.04),7.409 (4.31), 7.426 (3.07), 7.429 (3.18), 7.466 (2.24), 7.471 (2.76),7.482 (2.33), 7.486 (3.64), 7.490 (1.80), 7.502 (1.51), 7.506 (1.38),7.602 (1.44), 7.620 (2.38), 7.640 (1.22), 7.704 (2.67), 7.722 (4.38),7.725 (3.36), 7.742 (4.40), 7.779 (4.49), 7.783 (5.00), 7.797 (2.96),7.800 (2.76), 8.308 (3.76), 8.312 (3.84), 8.329 (3.56), 8.333 (3.38),8.612 (16.00), 9.161 (3.69), 9.182 (3.62). 84 LC-MS (Method L5): Rt =0.69 min; MS (ESIpos): m/z = 517 [M + H]+ 85 LC-MS (Method L5): Rt =1.38 min; MS (ESIpos): m/z = 564 [M + H]+ 86 LC-MS (Method L5): Rt =1.20 min; MS (ESIpos): m/z = 524 [M + H]+ 87 LC-MS (Method L5): Rt =1.25 min; MS (ESIpos): m/z = 519 [M + H]+ 88 1.3 LC-MS (Method L5): Rt =0.71 min; MS (ESIpos): m/z = 519 [M + H]+ 89 2.2 LC-MS (Method L5): Rt =0.95 min; MS (ESIpos): m/z = 506 [M + H]+ 90 4.9 LC-MS (Method L5): Rt =1.33 min; MS (ESIpos): m/z = 534 [M + H]+ 91 2.9 LC-MS (Method L5): Rt =1.12 min; MS (ESIpos): m/z = 546 [M + H]+ 92 2.9 LC-MS (Method L5): Rt =1.12 min; MS (ESIpos): m/z = 546 [M + H]+ 93 LC-MS (Method L5): Rt =1.33 min; MS (ESIpos): m/z = 564 [M + H]+ 94 LC-MS (Method L5): Rt =0.72 min; MS (ESIpos): m/z = 545 [M + H]+ 95 LC-MS (Method L5): Rt =0.96 min; MS (ESIpos): m/z = 532 [M + H]+ 96 1.4 LC-MS (Method L5): Rt =0.74 min; MS (ESIpos): m/z = 545 [M + H]+ 97 LC-MS (Method L5): Rt =1.01 min; MS (ESIpos): m/z = 544 [M + H]+ 98 LC-MS (Method L5): Rt =0.90 min; MS (ESIpos): m/z = 533 [M + H]+ 99-1 2.2 LC-MS (Method L5): Rt= 0.97 min; MS (ESIpos): m/z = 539 [M + H]+ 99-2 2.1 LC-MS (Method L5):Rt = 0.93 min; MS (ESIpos): m/z = 520 [M + H]+ 100 1.9 LC-MS (MethodL5): Rt = 0.87 min; MS (ESIpos): m/z = 492 [M + H]+ 101 1.8 LC-MS(Method L5): Rt = 0.85 min; MS (ESIpos): m/z = 518 [M + H]+ 102 LC-MS(Method L5): Rt = 0.85 min; MS (ESIpos): m/z = 504 [M + H]+ 103 LC-MS(Method L5): Rt = 0.71 min; MS (ESIpos): m/z = 557 [M + H]+ 104 LC-MS(Method L5): Rt = 1.26 min; MS (ESIpos): m/z = 516 [M + H]+ 105 LC-MS(Method L5): Rt = 1.27 min; MS (ESIpos): m/z = 516 [M + H]+ 106 3.7LC-MS (Method L5): Rt = 1.24 min; MS (ESIpos): m/z = 516 [M + H]+ 107LC-MS (Method L5): Rt = 1.31 min; MS (ESIpos): m/z = 546 [M + H]+ 108LC-MS (Method L5): Rt = 1.03 min; MS (ESIpos): m/z = 504 [M + H]+ 109LC-MS (Method L5): Rt = 1.42 min; MS (ESIpos): m/z = 564 [M + H]+ 110LC-MS (Method L5): Rt = 1.38 min; MS (ESIpos): m/z = 544 [M + H]+ 111LC-MS (Method L5): Rt = 1.00 min; MS (ESIpos): m/z = 550 [M + H]+ 1122.6 LC-MS ¹H-NMR 400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (3.14), 0.008(2.96), 0.146 (0.46), L1): Rt = 1.917 (0.92), 1.937 (0.96), 1.949(1.08), 1.10 min; 1.968 (0.98), 2.328 (0.72), 2.568 (1.52), MS 2.587(2.01), 2.605 (1.54), 2.624 (0.91), (ESIpos): 2.640 (0.62), 2.670(0.64), 2.849 (0.85), m/z = 538 2.868 (1.12), 2.887 (1.37), 2.908(0.64), [M + H]+ 2.974 (0.91), 2.988 (0.95), 3.707 (1.26), 3.726 (2.13),3.736 (2.13), 3.753 (1.19), 3.841 (2.10), 3.873 (4.31), 3.905 (2.01),5.508 (0.54), 5.528 (1.68), 5.549 (1.67), 7.224 (2.73), 7.233 (3.15),7.241 (3.80), 7.271 (2.34), 7.414 (1.68), 7.429 (1.43), 7.640 (16.00),7.665 (1.81), 7.684 (2.39), 7.705 (2.19), 7.835 (2.72), 7.850 (2.23),8.239 (2.35), 8.258 (2.17), 8.695 (9.00), 9.086 (2.09), 9.106 (2.05).113 LC-MS (Method L5): Rt = 1.04 min; MS (ESIpos): m/z = 545 [M + H]+114 LC-MS (Method L5): Rt = 1.40 min; MS (ESIpos): m/z = 566 [M + H]+115 LC-MS (Method L5): Rt = 1.05 min; MS (ESIpos): m/z = 533 [M + H]+116 3.4 LC-MS (Method L5): Rt = 1.25 min; MS (ESIpos): m/z = 559 [M +H]+ 117 LC-MS (Method L5): Rt = 1.25 min; MS (ESIpos): m/z = 565 [M +H]+ 118 LC-MS (Method L5): Rt = 1.33 min; MS (ESIpos): m/z = 552 [M +H]+ 119 LC-MS (Method L5): Rt = 0.92 min; MS (ESIpos): m/z = 506 [M +H]+ 120 LC-MS (Method L5): Rt = 0.94 min; MS (ESIpos): m/z = 502 [M +H]+ 121 LC-MS (Method L5): Rt = 1.00 min; MS (ESIpos): m/z = 524 [M +H]+ 122 2 LC-MS (Method L5): Rt = 0.90 min; MS (ESIpos): m/z = 547 [M +H]+ 123 LC-MS (Method L5): Rt = 0.98 min; MS (ESIpos): m/z = 544 [M +H]+ 124 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 0.007 (0.42),1.234 (0.43), 1.937 (0.49), L8): Rt = 1.954 (1.37), 1.962 (0.72), 1.971(1.46), 0.82 min; 1.979 (1.53), 1.988 (0.69), 1.996 (1.47), MS 2.013(0.54), 2.446 (0.68), 2.453 (0.82), (ESIpos): 2.462 (1.42), 2.469(1.84), 2.478 (2.17), m/z = 518 2.518 (7.50), 2.809 (0.67), 2.826(1.25), [M − H]− 2.842 (1.48), 2.858 (1.88), 2.874 (0.85), 2.960 (1.13),2.967 (1.21), 2.978 (1.24), 2.984 (1.18), 2.992 (0.89), 2.998 (0.84),3.009 (0.81), 3.016 (0.70), 3.316 (1.98), 3.664 (0.52), 3.675 (1.21),3.689 (2.49), 3.701 (2.76), 3.715 (2.35), 3.729 (1.06), 3.740 (0.44),5.503 (0.84), 5.519 (2.36), 5.535 (2.35), 5.551 (0.79), 6.929 (2.26),7.192 (0.72), 7.206 (4.09), 7.213 (4.86), 7.220 (5.20), 7.224 (3.60),7.235 (1.11), 7.255 (3.09), 7.266 (1.77), 7.271 (1.27), 7.362 (2.40),7.368 (2.53), 7.379 (2.23), 7.400 (2.23), 7.534 (2.37), 7.548 (3.14),7.550 (2.96), 7.565 (2.60), 7.599 (3.07), 7.603 (6.46), 7.607 (4.90),7.627 (16.00), 7.631 (11.94), 7.739 (3.66), 7.741 (3.78), 7.754 (3.17),7.755 (3.13), 7.917 (1.31), 7.928 (2.35), 7.938 (1.20), 8.157 (3.18),8.334 (3.01), 8.350 (2.81), 8.562 (10.41), 8.850 (3.16), 8.866 (3.04).125 2.1 LC-MS (Method L5): Rt = 0.95 min; MS (ESIpos): m/z = 542 [M +H]+ 126 LC-MS (Method L5): Rt = 0.87 min; MS (ESIpos): m/z = 533 [M +H]+ 127 1.9 LC-MS (Method L5): Rt = 0.90 min; MS (ESIpos): m/z = 519[M + H]+ 128 2.1 LC-MS (Method L5): Rt = 0.97 min; MS (ESIpos): m/z =520 [M + H]+ 129 1.8 LC-MS (Method L5): Rt = 0.85 min; MS (ESIpos): m/z= 505 [M + H]+ 130 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]:3.066 (16.00), 4.262 (0.81), L1): Rt = 4.270 (0.92), 5.754 (1.15), 6.784(0.98), 0.85 min; 6.787 (1.02), 6.805 (1.10), 6.807 (1.10), MS 6.923(0.99), 6.926 (0.97), 7.169 (0.81), (ESIpos): 7.353 (0.82), 7.373(0.79), 7.455 (0.88), m/z = 458 7.460 (1.48), 7.464 (1.00), 7.469(1.06), [M + H]+ 7.487 (1.54), 7.506 (0.70), 7.532 (0.80), 7.536 (1.38),7.540 (0.75), 7.554 (0.76), 7.623 (0.73), 7.643 (2.49), 7.648 (1.12),7.662 (1.03), 7.739 (1.15), 7.743 (1.22), 7.757 (0.88), 7.761 (0.82),8.204 (1.00), 8.208 (1.02), 8.225 (0.96), 8.229 (0.88), 8.611 (3.90),9.078 (0.87), 9.098 (0.85). 131 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (2.45), 0.008 (2.01), 2.031 (0.91), L1): Rt = 2.038(0.84), 2.086 (1.12), 2.199 (0.70), 1.40 min; 3.673 (16.00), 3.742(5.31), 4.174 (1.20), MS 4.181 (0.78), 4.195 (0.87), 4.203 (0.99),(ESIpos): 4.287 (0.82), 4.296 (0.76), 4.304 (0.93), m/z = 494 5.125(1.08), 5.142 (1.08), 6.796 (1.69), [M + H]+ 6.816 (1.95), 6.878 (0.99),6.881 (0.91), 6.897 (1.97), 6.916 (1.18), 6.957 (0.91), 6.972 (0.89),7.152 (1.31), 7.157 (1.12), 7.166 (1.84), 7.171 (2.18), 7.185 (2.45),7.196 (1.01), 7.206 (1.77), 7.283 (0.80), 7.287 (0.91), 7.294 (1.69),7.314 (1.54), 7.387 (2.01), 7.391 (1.99), 7.406 (1.77), 7.409 (1.59),7.445 (2.22), 7.449 (2.24), 7.501 (6.85), 7.506 (6.87), 7.717 (0.85),7.736 (1.54), 7.741 (2.47), 7.746 (1.27), 7.935 (2.81), 7.951 (2.83),8.166 (0.63), 8.903 (1.69), 8.921 (1.69), 9.904 (1.94), 9.922 (2.56),9.934 (1.42). 132 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (1.84), 0.008 (1.78). 3.075 L6): Rt = (16.00), 4.248 (0.91),4.256 (1.05), 6.774 2.15 min; (1.08), 6.777 (1.18), 6.794 (1.23), 6.797MS (1.29), 6.889 (0.56), 6.905 (1.13), 6.908 (ESIpos): (1.14), 6.924(0.71), 6.926 (0.68), 7.142 m/z = 526 (0.63), 7.160 (0.95), 7.335(0.74), 7.468 [M + H]+ (0.66), 7.474 (0.64), 7.633 (0.61), 7.650 (1.67),7.669 (2.82), 7.900 (2.22), 7.906 (2.18), 8.257 (1.14), 8.263 (1.06),8.276 (1.03), 8.282 (1.00), 8.537 (3.81). 133 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.91), −0.008 (7.68), 0.008 L6): Rt =(7.18), 0.146 (0.91), 2.027 (1.24), 2.035 2.40 min; (1.27), 2.046(1.34), 2.062 (1.88), 2.070 MS (1.58), 2.078 (1.17), 2.085 (0.81), 2.184(ESIpos): (1.24), 2.196 (1.71), 2.209 (1.71), 2.218 m/z = 568 (1.64),2.230 (1.07), 2.366 (0.70), 2.710 [M + H]+ (0.64), 3.247 (1.24), 3.289(8.35), 3.334 (1.81), 3.866 (8.18), 3.876 (13.05), 3.888 (7.51), 3.906(0.97), 4.204 (0.74), 4.212 (0.97), 4.224 (0.91), 4.232 (2.85), 4.240(2.28), 4.252 (3.66), 4.264 (3.52), 4.271 (2.52), 4.280 (2.52), 4.299(0.94), 5.241 (2.11), 5.255 (2.08), 5.753 (4.53), 6.776 (4.49), 6.779(5.00), 6.796 (5.20), 6.799 (5.50), 6.896 (2.21), 6.915 (4.70), 6.933(2.78), 7.142 (2.55), 7.147 (2.72), 7.164 (4.13), 7.181 (2.11), 7.186(2.01), 7.357 (4.19), 7.374 (3.96), 7.444 (2.25), 7.450 (2.42), 7.476(2.68), 7.482 (2.58), 7.686 (1.38), 7.703 (7.55), 7.711 (6.74), 7.720(16.00), 7.728 (1.71), 7.909 (7.31), 7.915 (7.11), 8.282 (0.91), 8.291(4.49), 8.300 (3.82), 8.307 (3.66), 8.316 (3.89), 8.325 (0.74), 8.606(7.01), 8.610 (7.75), 9.160 (2.82), 9.181 (2.72). 134 1.9 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ (Method [ppm] = 8.99 (d, 1H), 8.45 (s, 1H), 8.36L1): Rt = (d, 1H), 8.13 (s, 1H), 7.83 (br s, 1H), 0.84 min; 7.73 (d,1H), 7.60-7.63 (m, 3H), 7.54 MS (t, 1H), 7.32 (d, 1H), 7.16 (t, 1H),6.91 (ESIpos): (t, 1H), 6.79 (d, 1H), 5.21-5.27 (m, m/z = 578 1H),4.22-4.30 (m, 2H), 3.07 (d, 3H), [M + H]+ 2.52-2.55 (m, 4H), 2.12-2.20(m, 1H), 2.00-2.08 (m, 1H). 135 1.9 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (6.30), 0.008 (2.98), 2.004 (1.02), L1): Rt =2.014 (0.94), 2.026 (1.43), 2.041 (1.28), 0.89 min; 2.126 (1.31), 2.141(1.56), 2.373 (2.15), MS 2.394 (2.92), 2.412 (2.16), 2.433 (1.25),(ESIpos): 2.519 (4.80), 2.523 (4.67), 4.243 (3.28), m/z = 504 4.255(4.75), 4.261 (3.01), 4.270 (2.58), [M + H]+ 4.427 (5.50), 4.446 (8.06),4.466 (4.62), 5.160 (0.92), 5.174 (1.75), 5.194 (1.64), 5.754 (2.42),6.781 (3.04), 6.785 (3.14), 6.802 (3.39), 6.805 (3.26), 6.887 (1.73),6.890 (1.66), 6.906 (3.30), 6.909 (2.99), 6.924 (1.93), 6.927 (1.70),7.142 (1.75), 7.146 (1.77), 7.163 (2.63), 7.180 (1.31), 7.185 (1.20),7.291 (2.83), 7.311 (2.52), 7.434 (2.40), 7.452 (3.13), 7.455 (2.90),7.473 (2.61), 7.592 (2.65), 7.597 (4.87), 7.602 (5.82), 7.611 (16.00),7.616 (8.48), 7.698 (3.62), 7.701 (3.63), 7.716 (3.07), 7.719 (2.82),8.058 (3.06), 8.061 (3.05), 8.080 (2.76), 8.083 (2.47), 8.430 (11.34),8.946 (2.94), 8.966 (2.74). 136 2.1 LC-MS ¹H-NMR (400 MHz, CHLOROFORM-d)(Method δ [ppm]: −0.008 (1.56), 0.008 (1.98), L1): Rt = 0.069 (0.62),1.256 (1.23), 1.582 (16.00), 0.93 min; 2.171 (1.20), 2.177 (0.59), 5.299(1.83), MS 6.997 (0.57), 7.429 (0.69), 7.519 (1.23). (ESIpos): m/z = 541[M + H]+ 137 4.8 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(2.04), 0.008 (1.38), 1.199 (3.32), L1): Rt = 1.216 (7.07), 1.234(3.34), 2.086 (1.65), 1.42 min; 3.048 (8.16), 4.052 (4.09), 4.134(0.95), MS 4.152 (2.94), 4.169 (2.79), 4.187 (0.86), (ESIpos): 4.283(1.07), 6.790 (1.19), 6.793 (1.25), m/z = 564 6.810 (1.31), 6.813(1.32), 6.917 (1.20), [M + H]+ 6.920 (1.17), 7.175 (0.96), 7.378 (0.94),7.645 (16.00), 7.689 (0.97), 7.707 (1.22), 7.710 (1.08), 7.728 (1.19),7.840 (1.33), 7.843 (1.41), 7.858 (1.10), 7.861 (1.03), 8.354 (1.21),8.358 (1.23), 8.375 (1.10), 8.379 (1.01), 8.756 (4.67), 9.196 (1.08),9.217 (1.02). 138 2.7 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method2.087 (0.95), 2.095 (0.79), 2.206 (0.84), L1): Rt = 2.218 (0.81), 2.228(0.77), 3.056 (16.00), 1.12 min; 3.516 (1.41), 3.529 (3.23), 3.541(2.52), MS 3.601 (1.41), 3.614 (2.77), 3.628 (2.42), (ESIpos): 3.641(0.85), 4.245 (1.32), 4.253 (1.18), m/z = 522 4.265 (2.15), 4.274(2.23), 4.290 (1.20), [M + H]+ 5.100 (1.14), 5.115 (2.39), 5.130 (1.09),5.279 (1.29), 5.298 (1.29), 5.752 (1.32), 5.754 (1.27), 6.792 (2.55),6.813 (2.83), 6.910 (1.24), 6.928 (2.57), 6.947 (1.49), 7.159 (1.29),7.176 (2.06), 7.197 (0.97), 7.357 (2.18), 7.376 (1.99), 7.625 (2.25),7.628 (2.63), 7.631 (3.12), 7.634 (5.58), 7.638 (12.01), 7.640 (9.99),7.643 (5.84), 7.646 (4.00), 7.665 (1.93), 7.801 (2.81), 7.819 (2.22),8.275 (2.37), 8.296 (2.15), 8.673 (7.74), 9.303 (2.25), 9.323 (2.20).139 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (Method (d, J = 8.2 Hz, 1H),8.58 (s, 1H), 8.29, L2): Rt = (dd, J = 9.4, 6.2 Hz, 1H), 7.77-7.68 (m,3.33 min; 2H), 7.61 (t, J = 9.3 Hz, 1H), 7.47-7.41 m/z = (m, 1H),7.37-7.31 (m, 1H), 7.20-7.13 510/512 (m, 1H), 6.95-6.88 (m, 1H),6.82-6.77 [M + H]+ (m, 1H). 5.27-5.19 (m, 1H), 4.30-4.19 (m, 2H), 3.07(s, 6H), 2.27-2.12 (m, 1H), 2.07-1.99 (m, 1H). 140 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 9.07 (Method (d, J = 8.2 Hz, 1H). 8.58 (s, 1H), 8.27,L2): Rt = (dd, J = 9.4, 6.2 Hz, 1H), 7.64-7.48 (m, 2.98 min; 3H), 7.34(d, J = 6.9 Hz, 1H), 7.31-7.23 m/z = 478 (m, 1H), 7.20-7.13 (m, 1H),6.95-6.88 [M + H]+ (m, 1H), 6.82-6.76 (m, 1H), 5.28-5.20 (m, 1H),4.32-4.19 (m, 2H), 3.06 (s, 6H), 2.22-2.14 (m, 1H), 2.09-1.99 (m, 1H).141 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (Method (d, J = 8.2 Hz, 1H).8.58 (s, 1H), 8.27, L2): Rt = (dd, J = 9.4, 6.2 Hz, 1H), 7.60 (t, J =9.3 3.03 min; Hz, 1H), 7.55-7.45 (m, 3H), 7.43-7.31 m/z = 476 (m, 2H),7.20-7.12 (m, 1H), 6.95-6.88 [M + H]+ (m, 1H), 6.83-6.76 (m, 1H),5.28-5.19 (m, 1H), 4.32-4.19 (m, 2H), 3.07 (s, 6H), 2.25-2.14 (m, 1H),2.09-1.98 (m, 1H). 142 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.17 (Method(d, J = 8.2 Hz, 1H). 8.67 (s, 1H), 8.34, L2): Rt = (dd, J = 9.4, 6.2 Hz,1H), 7.66 (t, J = 9.3 3.68 min; Hz, 1H), 7.40-7.28 (m, 2H), 7.22-7.13m/z = 520 (m, 3H), 6.96-6.89 (m, 1H), 6.82-6.76 [M + H]+ (m, 1H),5.29-5.21 (m, 1H), 4.33-4.19 (m, 2H), 3.88 (q, J = 5.8, 4.5 Hz, 4H),3.28 (q, J = 4.5 Hz, 4H), 2.27-2.16 (m, 1H), 2.10-2.00 (m, 1H). 143LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.17 (Method (d, J = 8.1 Hz, 1H), 8.68(s, 1H), 8.34, L2): Rt = (dd, J = 9.4, 6.2 Hz, 1H), 7.66 (t, J = 9.33.86 min; Hz, 1H), 7.55-7.49 (m, 1H), 7.40-7.29 m/z = 536 (m, 3H),7.21-7.13 (m, 1H), 6.96-6.89 [M + H]+ (m, 1H), 6.82-6.76 (m, 1H),5.29-5.21 (m, 1H), 4.33-4.19 (m, 2H), 3.87 (t, J = 4.5 Hz, 4H), 3.28 (q,J = 4.6 Hz, 4H), 2.26-2.18 (m, 1H), 2.11-2.02 (m, 1H). 144 LC-MS ¹H-NMR(400 MHz, Chloroform-d) δ (Method 8.85 (s, 1H), 7.83 (dd, J = 9.8, 2.9Hz, L2): Rt = 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.55 (d, 4.14 min; J = 8.3Hz, 1H), 7.50 (dd, J = 8.6, 2.9 m/z = Hz, 1H), 7.45 (dd, J = 8.3, 2.0Hz, 1H), 552/554 7.29 (d, J = 7.7 Hz, 1H), 7.26-7.17 (m, [M + H]+ 1H),6.94 (td, J = 7.5, 1.1 Hz, 1H), 6.87 (dd, J = 8.3, 1.0 Hz, 1H), 6.82 (d,J = 7.3 Hz, 1H), 5.38 (d, J = 7.3 Hz, 1H), 4.36 (dq, J = 9.2, 3.4, 2.9Hz, 1H), 4.20 (ddd, J = 11.6, 9.6, 2.7 Hz, 1H), 3.97- 3.84 (m, 4H),3.44-3.33 (m, 4H), 2.47- 2.35 (m, 1H), 2.29-2.19 (m, 1H). 145 LC-MS¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.89 (s, 1H), 7.76 (dd, J =9.9, 2.9 Hz, L2): Rt = 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.54 (d, 3.82 min;J = 8.3 Hz, 1H), 7.49-7.43 (m, 2H), m/z = 7.29 (d, J = 7.7 Hz, 1H),7.24-7.18 (m, 510/512 1H), 7.08 (d, J = 7.5 Hz, 1H), 6.93 (td, [M + H]+J = 7.5, 1.1 Hz, 1H), 6.88-6.84 (m, 1H), 5.40-5.33 (m, 1H). 4.38-4.31(m, 1H), 4.23-4.16 (m, 1H), 3.10 (s, 6H), 2.44-2.34 (m, 1H), 2.25-2.16(m, 1H). 146 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.85 (d, J =2.7 Hz, 1H), 7.81 (dd, J = L2): Rt = 10.0, 2.8 Hz, 1H), 7.54 (dd, J =7.9, 3.55 min; 1.6 Hz, 1H), 7.40 (dd, J = 8.3, 2.8 Hz, m/z = 1H),7.34-7.15 (m, 4H), 7.07-6.97 (m, 510/512 1H), 6.91 (td, J = 7.5, 1.1 Hz,1H), [M + H]+ 6.85 (dd, 1H), 5.40-5.29 (m, 1H), 4.37- 4.30 (m, 1H),4.22-4.14 (m, 1H), 3.12 (s, 6H), 2.43-2.32 (m, 1H), 2.23-2.14 (m, 1H).147 2.76 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.121 (0.91); 9.1007 (0.93);8.634 (3.89); 8.3134 (0.72); 8.2547 (0.98); 8.2517 (1.05); 8.2336(1.09); 8.2306 (1.1); 7.805 (1.01); 7.7903 (1.21); 7.7874 (1.21); 7.6694(1.03); 7.6485 (1.18); 7.6304 (12.69); 6.8945 (1.38); 6.8875 (1.57);6.7982 (0.58); 6.7911 (0.47); 6.7761 (1.29); 6.7688 (1.22); 6.7441(2.53); 6.7219 (1.02); 5.2287 (0.58); 5.2095 (0.58); 4.2178 (0.58);4.2045 (1.04); 4.1982 (0.85); 4.1864 (0.55); 4.1782 (0.56); 3.6948(11.21); 3.3162 (70.62); 3.2923 (0.36); 3.0725 (16); 2.6745 (0.55);2.6703 (0.76); 2.6659 (0.57); 2.5055 (89.32); 2.5011 (123.65); 2.4967(94.57); 2.3324 (0.52); 2.328 (0.71); 2.3236 (0.52); 2.1952 (0.33);2.185 (0.35); 2.1736 (0.35); 2.0579 (0.35); 2.0505 (0.41); 1.3981(6.55); 0.1458 (0.5); 0.008 (4.19); −0.0001 (108.21); −0.0083 (4.43);−0.1497 (0.5) 148 2.84 ¹H-NMR (399, 9532 MHz, DMSO): δ = 8.8981 (0.68),8.8777 (0.7), 8.6125 (3.39), 8.3132 (0.55), 8.2499 (0.74), 8.2465(0.82), 8.2286 (0.85), 8.2252 (0.85), 7.805 (0.71), 7.8016 (0.8), 7.7871(0.96), 7.7838 (0.98), 7.6657 (0.85), 7.6476 (0.82), 7.6444 (0.97),7.6324 (11.7), 7.3105 (0.9), 7.2897 (1), 6.8463 (0.92), 6.8409 (1.09),6.7994 (0.64), 6.7934 (0.54), 6.7787 (0.58), 6.7727 (0.53), 5.4719(0.54), 5.4526 (0.54), 3.7345 (9.41), 3.3174 (129.06), 3.0587 (12.87),3.0247 (0.38), 2.8426 (0.45), 2.8226 (0.35), 2.6747 (0.57), 2.6702(0.79), 2.6658 (0.58), 2.5368 (0.56), 2.5237 (2.21), 2.5101 (44.34),2.5056 (94.37), 2.5011 (132.67), 2.4965 (99.85), 2.4921 (48.15), 2.3324(0.55), 2.3281 (0.77), 2.3234 (0.56), 1.398 (16), 0.1459 (0.57), 0.008(4.36), −0.0002 (135.3), −0.0084 (4.88), −0.1496 (0.56) 148 2.2 LC-MS¹H-NMR (400 MHz, CHLOROFORM- (Method d) δ [ppm]: 2.171 (1.43), 2.631(16.00), L1): Rt = 3.229 (12.71), 3.305 (1.03), 3.313 (1.03), 0.94 min;4.269 (0.86), 6.828 (1.34), 6.830 (1.40), MS 6.848 (1.53), 6.851 (1.54),6.950 (1.41), (ESIneg): 6.953 (1.37), 6.969 (0.85), 6.972 (0.79), m/z =589 7.198 (1.15), 7.327 (1.22), 7.346 (1.12), [M − H]− 7.390 (1.53),7.395 (2.99), 7.400 (1.71), 7.512 (6.31), 7.517 (5.89), 7.551 (0.97),7.569 (1.53), 7.572 (1.24), 7.590 (1.44), 7.661 (1.63), 7.665 (1.74),7.679 (1.23), 7.683 (1.12), 8.058 (1.46), 8.062 (1.45), 8.079 (1.31),8.083 (1.23), 8.983 (5.10). 150 3.1 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method 2.132 (1.28), 2.205 (1.37), 2.328 (0.59), L1): Rt = 3.040(16.00), 3.931 (0.61), 3.975 (4.59), 1.11 min; 3.984 (4.71), 4.281(3.48), 5.309 (1.69), MS 5.326 (1.68), 6.779 (2.78), 6.799 (3.08),(ESIpos): 6.883 (1.42), 6.901 (2.80), 6.920 (1.72), m/z = 536 7.140(1.56), 7.159 (2.50), 7.175 (1.25), [M + H]+ 7.348 (2.66), 7.365 (2.47),7.643 (14.76), 7.660 (2.25), 7.678 (2.82), 7.699 (1.88), 7.820 (3.02),7.835 (2.42), 8.139 (1.05), 8.304 (2.56), 8.326 (2.33), 8.755 (6.56).151 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (0.73),0.008 (0.73), 2.827 (5.86), L6): Rt = 2.831 (9.97), 2.836 (5.88), 3.063(16.00), 1.55 min; 4.234 (0.56), 4.253 (0.85), 4.262 (0.92), MS 6.778(0.94), 6.781 (1.01), 6.799 (1.07), (ESIpos): 6.801 (1.08), 6.894(0.49), 6.897 (0.49), m/z = 503 6.912 (1.00), 6.915 (0.97), 6.931(0.61), [M + H]+ 6.934 (0.57), 7.026 (0.55), 7.043 (0.90), 7.055 (1.02),7.060 (0.67), 7.082 (0.74), 7.142 (0.50), 7.146 (0.54), 7.164 (0.80),7.339 (0.78), 7.359 (0.78), 7.606 (0.49), 7.623 (1.27), 7.643 (1.95),7.650 (1.53), 7.663 (0.52), 8.214 (0.96), 8.220 (0.91), 8.234 (0.91),8.240 (0.83), 8.542 (4.00), 9.073 (0.89), 9.093 (0.86). 152 3 ¹H-NMR(399, 9532 MHz, DMSO): δ = 9.0892 (0.94); 9.0691 (0.96); 8.6414 (4.26);8.2521 (0.97); 8.2488 (1.02); 8.2308 (1.12); 8.2275 (1.08); 7.8117(0.96); 7.8084 (1.01); 7.7939 (1.28); 7.7906 (1.21); 7.6681 (1.04); 7.65(1.06); 7.6469 (1.19); 7.633 (11.43); 7.4321 (0.64); 7.4139 (0.79);7.411 (0.8); 7.3933 (0.66); 6.7953 (0.48); 6.7887 (0.52); 6.774 (0.91);6.7673 (0.95); 6.7527 (0.46); 6.746 (0.48); 6.6796 (0.98); 6.673 (0.85);6.6532 (1.02); 6.6466 (0.82); 5.7538 (9.65); 5.2288 (0.51); 5.2099(0.52); 4.315 (0.48); 4.3057 (0.46); 4.2996 (0.54); 4.2881 (0.57);4.2791 (0.52); 4.2653 (0.45); 4.2581 (0.58); 3.3173 (12.38); 3.0582(16); 2.5238 (0.61); 2.5104 (12.16); 2.5059 (24.77); 2.5014 (33.92);2.4969 (25.2); 2.4926 (12.16); 2.1993 (0.33); 2.1898 (0.34); 2.177(0.37); 2.078 (0.34); 2.0714 (0.39); 0.008 (1.15); −0.0002 (30.44);−0.0084 (1.11) 153 2.1 LC-MS ¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: (Method1.241 (8.09), 1.253 (15.76), 1.265 (7.87), L1): Rt = 2.024 (1.23), 2.030(1.43), 2.037 (1.48), 0.92 min; 2.046 (1.79), 2.053 (1.70), 2.146(1.59), MS 2.157 (1.87), 2.166 (1.55), 3.508 (1.58), (ESIpos): 3.519(4.30), 3.530 (5.43), 3.540 (4.15), m/z = 492 3.552 (1.33), 4.266(5.31), 4.273 (4.37), [M + H]+ 4.292 (0.68), 5.238 (1.23), 5.248 (2.59),5.260 (2.52), 5.270 (1.13), 6.788 (4.52), 6.802 (4.77), 6.899 (2.30),6.912 (4.55), 6.924 (2.56), 7.152 (2.32), 7.165 (3.89), 7.177 (1.93),7.302 (4.05), 7.315 (3.75), 7.522 (2.63), 7.535 (4.17), 7.548 (2.83),7.606 (6.74), 7.620 (16.00), 7.662 (0.48), 7.731 (4.94), 7.743 (4.36),7.808 (2.02), 7.816 (3.34), 8.412 (4.22), 8.426 (4.01), 8.509 (10.45),9.013 (4.02), 9.027 (3.89). 154 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.149 (0.40), −0.008 (3.14), 0.008 L1): Rt = (2.78), 0.833(0.80), 0.851 (1.18), 1.028 0.97 min; (0.44), 1.103 (0.60), 1.118(0.70), 1.235 MS (1.90), 1.874 (16.00), 1.914 (1.00), 2.063 (ESIpos):(0.78), 2.108 (1.12), 2.163 (0.90), 2.366 m/z = 521 (0.68), 2.518(4.57), 2.523 (3.14), 2.709 [M + H]+ (0.54), 3.508 (0.82), 4.232 (0.58),4.249 (1.20), 4.258 (1.14), 4.275 (1.58), 4.293 (0.98), 4.302 (1.16),5.233 (0.52), 5.249 (1.04), 5.266 (1.08), 6.776 (2.22), 6.794 (2.46),6.877 (1.16), 6.893 (2.38), 6.911 (1.44), 7.135 (1.28), 7.155 (2.02),7.174 (1.06), 7.340 (1.82), 7.359 (1.74), 7.574 (1.36), 7.592 (1.96),7.617 (4.01), 7.622 (5.21), 7.628 (11.15), 7.633 (5.41), 7.726 (0.58),7.789 (2.38), 7.805 (2.08), 8.516 (1.20), 8.538 (1.18), 8.604 (3.14),9.016 (1.62), 9.036 (1.58), 9.575 (0.84), 10.034 (0.98). 155 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.17 (Method (dd, J = 8.1, 4.5 Hz, 1H), 8.64(d, J = 2.4 L2): Rt = Hz, 1H), 8.37 (dd, J = 9.4, 6.3 Hz, 1H), 3.77 min;7.74-7.64 (m, 2H), 7.47-7.32 (m, 3H), MS 7.20-7.12 (m, 1H), 6.95-6.88(m, 1H), (ESIpos): 6.82-6.76 (m, 1H), 5.29-5.20 (m, 1H), m/z = 5364.32-4.18 (m, 2H), 3.93-3.83 (m, 4H), [M + H]+ 3.31-3.22 (m, 4H),2.27-2.16 (m, 1H), 2.10-2.01 (m, 1H). 156 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.17 (Method (d, J = 8.1 Hz, 1H), 8.66 (s, 1H), 8.33 L2): Rt= (dd, J = 9.4, 6.2 Hz, 1H), 7.79-7.62 (m, 3.96 min; 3H), 7.47-7.42 (m,1H), 7.40-7.34 m/z = (m, 1H), 7.21-7.13 (m, 1H), 6.96-6.89 552/554 (m,1H), 6.83-6.76 (m, 1H), 5.29-5.21 [M + H]+ (m, 1H), 4.33-4 19 (m, 2H),3.91-3.83 (m, 4H), 3.30-3.23 (m, 4H), 2.25-2.19 (m, 1H), 2.10-2.02 (m,1H). 157 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.16 (Method (d, J = 8.1 Hz,1H), 8.66 (s, 1H), 8.36- L2): Rt = 8.28 (m, 1H), 7.65 (t, J = 9.3 Hz,1H), 3.61 min; 7.54 (q, J = 8.7 Hz, 2H), 7.41-7.25 (m, m/z = 520 2H),7.21-7.13 (m, 1H), 6.92 (t, J = [M + H]+ 7.1 Hz, 1H), 6.79 (d, J = 8.1Hz, 1H), 525 (q, J = 5.7 Hz, 1H), 4.33-4.19 (m, 2H), 3.93-3.82 (m, 4H),3.31-3.21 (m, 4H), 2.21 (dt, J = 8.6, 4.4 Hz, 1H), 2.11-2.00 (m, 1H).158 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.86 (s, 1H), 7.82(dd, J = 9.8, 2.9 Hz, L2): Rt = 1H), 7.52-7.44 (m, 2H), 7.36-7.19 3.85min; (m, 4H), 6.93 (td, J = 7.5, 1.1 Hz, 1H), m/z = 520 6.89-6.80 (m,2H), 5.43-5.34 (m, 1H), [M + H]+ 4.41-4.32 (m, 1H), 4.24-4.15 (m, 1H),3.96-3.84 (m, 4H), 3.44-3.33 (m, 4H), 2.46-2.36 (m, 1H), 2.28-2.19 (m,1H). 159 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.85 (s, 1H),7.81 (dd, J = 9.8, 2.9 Hz, L2): Rt = 1H), 7.62-7.59 (m, 1H), 7.52-7.383.95 min; (m, 4H), 7.28 (d, J = 7.7 Hz, 1H), m/z = 518 7.24-7.18 (m,1H), 6.96-6.83 (m, 3H), [M + H]+ 5.43-5.30 (m, 1H), 4.40-4.31 (m, 1H),4.25-4.15 (m, 1H), 3.96-3.83 (m, 4H), 3.44-3.31 (m, 4H), 2.45-2.34 (m,1H), 2.28-2.17 (m, 1H). 160 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.83 (s, 1H), 7.87 (dd, J = 9.8, 2.9 Hz, L2): Rt = 1H),7.53-7.46 (m, 2H), 7.34-7.26 3.91 min; (m, 2H), 7.24-7.17 (m, 2H), 6.92(td, m/z = 536 J = 7.5, 1.2 Hz, 1H), 6.89-6.80 (m, 2H), [M + H]+5.40-5.33 (m, 1H), 4.39-4.31 (m, 1H), 4.23-4.12 (m, 1H), 3.96-3.84 (m,4H), 3.44-3.33 (m, 4H), 2.44-2.34 (m, 1H), 2.26-2.18 (m, 1H). 161 LC-MS¹H-NMR (400 MHz, Chlofoform-d) δ (Method 8.82 (s, 1H), 7.89 (dd, J =9.8, 2.9 Hz, L2): Rt = 1H), 7.45 (dd, J = 8.3, 2.9 Hz, 1H), 3.83 min;7.37-7.18 (m, 4H), 7.14 (d, J = 7.5 Hz, m/z = 536 1H), 6.92 (td, J =7.5, 1.2 Hz, 1H), 6.86 [M + H]+ (dd, J = 8.3, 1.0 Hz, 1H), 6.79 (s, 1H),5.41-5.34 (m, 1H), 4.39-4.31 (m, 1H), 4.22-4.14 (m, 1H), 3.97-3.87 (m,4H), 3.47-3.34 (m, 4H), 2.45-2.35 (m, 1H), 2.26-2.18 (m, 1H). 162 LC-MS¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.86 (s, 1H), 7.84 (dd, J =9.1, 2.9 Hz, L2): Rt = 1H), 7.51 (dd, J = 8.6, 2.9 Hz, 1H), 3.89 min;7.29 (d, J = 7.7 Hz, 1H), 7.24-7.12 m/z = 520 (m, 3H), 6.97-6.78 (m,4H), 5.42-5.34 [M + H]+ (m, 1H), 4.40-4.32 (m, 1H), 4.24-4.15 (m, 1H),3.96-3.85 (m, 4H), 3.44-3.33 (m, 4H), 2.46-2.36 (m, 1H), 2.29-2.19 (m,1H). 163 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.85 (s, 1H),7.84 (dd, J = 9.7, 2.8 Hz, L2): Rt = 1H), 7.50 (dd, J = 8.5, 2.8 Hz,1H), 4.05 min; 7.39 (s, 1H), 7.32-7.13 (m, 4H), 6.94 m/z = 536 (t, J =7.1 Hz, 1H), 6.90-6.80 (m, 2H), [M + H]+ 5.42-5.34 (m, 1H), 4.41-4.32(m, 1H), 4.24-4.15 (m, 1H), 3.96-3.84 (m, 4H), 3.44-3.32 (m, 4H),2.46-2.35 (m, 1H), 2.29-2.19 (m, 1H). 164 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.83 (s, 1H), 7.86 (dd, J = 9.8, 2.9 Hz, L2): Rt= 1H), 7.51 (dd, J = 8.3, 2.7 Hz, 1H), 3.94 min; 7.44-7.36 (m, 2H), 7.28(d, J = 7.8 Hz, m/z = 536 1H), 7.23-7.18 (m, 1H), 7.14 (t, J = [M + H]+8.9 Hz, 1H), 6.92 (td, J = 7.5, 1.1 Hz, 1H), 6.89-6.81 (m, 2H),5.41-5.32 (m, 1H), 4.39-4.30 (m, 1H), 4.23-4.14 (m, 1H), 3.95-3.84 (m,4H), 3.44-3.33 (m, 4H), 2.45-2.33 (m, 1H), 2.27-2.16 (m, 1H). 165 LC-MS¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.83 (s, 1H), 7.87 (dd, J =9.9, 2.8 Hz, L2): Rt = 1H), 7.44 (dd, J = 8.3, 2.8 Hz, 1H), 3.82 min;7.34-7.26 (m, 3H), 7.24-7.18 (m, 1H), m/z = 536 7.10 (td, J = 8.2, 2.5Hz, 1H), 6.92 [M + H]+ (t, J = 7.5 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H),6.80 (d, J = 5.9 Hz, 1H), 5.43- 5.30 (m, 1H), 4.39-4.31 (m, 1H),4.22-4.14 (m, 1H), 3.96-3.86 (m, 4H), 3.46-3.34 (m, J = 3.8 Hz, 4H),2.45- 2.35 (m, 1H), 2.27-2.17 (m, 1H). 166 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.80 (s, 1H), 7.87 (dd, J = 9.8, 2.9 Hz, L2): Rt= 1H), 7.55 (dd, J = 8.0, 1.6 Hz, 1H), 3.95 min; 7.43 (dd, J = 8.2, 2.8Hz, 1H), 7.33-7.17 m/z = (m, 4H), 6.94-6.77 (m, 3H), 5.41-5.30 552/554(m, 1H), 4.37-4.31 (m, 1H), 4.21-4.14 [M + H]+ (m, 1H), 3.95-3.85 (m,4H), 3.45-3.33 (m, 4H), 2.44-2.34 (m, 1H), 2.25-2.16 (m, 1H). 167 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.17 (Method (d, J = 8.2 Hz, 1H), 8.66 (s,1H), 8.32, L2): Rt = (dd, J = 9.4.6.2 Hz, 1H), 7.65 (t, J = 9.3 3.68min; Hz, 1H), 7.56-7.47 (m, 3H), 7.43-7.34 m/z = 518 (m, 2H), 7.21-7.14(m, 1H), 6.97-6.89 [M + H]+ (m, 1H), 6.80 (d, J = 8.2, 0.9 Hz, 1H),5.30-5.22 (m, 1H), 4.33-4.19 (m, 2H), 3.88 (t, J = 4.6 Hz, 4H),3.32-3.22 (m, 4H), 2.28-2.17 (m, 1H), 2.11-1.98 (m, 1H). 168 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (Method (d, J = 8.2 Hz, 1H), 8.59 (s,1H), 8.33- L2): Rt = 8.25 (m, 1H), 7.60 (t, J = 9.3 Hz, 1H), 3.07 min;7.38-7.27 (m, 2H), 7.22-7.12 (m, 3H), m/z = 478 6.95-6.88 (m, 1H),6.82-6.76 (m, 1H), [M + H]+ 5.27-5.19 (m, 1H), 4.32-4.19 (m, 2H), 3.07(s, 6H), 2.25-2.14 (m, 1H), 2.09-1.98 (m, 1H). 169 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 9.08 (Method (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.33-L2): Rt = 8.26 (m, 1H), 7.61 (t, J = 9.3 Hz, 1H), 3.26 min; 7.54-7.49(m, 1H), 7.39-7.28 (m, 3H), m/z = 494 7.20-7.13 (m, 1H), 6.95-6.88 (m,1H), [M + H]+ 6.82-6.76 (m, 1H), 5.27-5.19 (m, 1H), 4.32-4.19 (m, 2H),3.07 (s, 6H), 2.25- 2.14 (m, 1H), 2.09-1.99 (m, 1H). 170 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 9.17 (Method (dd, J = 8.1, 3.6 Hz, 1H), 8.66 (d, J= L2): Rt = 1.2 Hz, 1H), 8.37 (dd, J = 9.4, 6.3 Hz, 3.82 min; 1H), 7.68(t, J = 9.1 Hz, 1H), 7.63-7.49 m/z = 536 (m, 2H), 7.46-7.34 (m, 2H),7.17 (t, J = [M + H]+ 7.7 Hz, 1H), 6.92 (t, J = 7.2 Hz, 1H), 6.80 (d, J= 82 Hz, 1H), 5.30-5.21 (m, 1H), 4.33-4.19 (m, 2H), 3.88 (t, J = 4.3 Hz,4H), 3.32-3.23 (m, 4H), 2.21 (d, J = 3.1 Hz, 1H), 2.06 (d, J = 6.4 Hz,1H). 171 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (Method (dd, J = 8.1,4.3 Hz, 1H), 8.56 (d, J = L2): Rt = 1.2, Hz, 1H), 8.34 (dd, J = 9.4, 6.3Hz, 3.23 min; 1H), 7.74-7.59 (m, 2H), 7.46-7.31 (m, m/z = 494 3H), 7.16(t, J = 7.1 Hz, 1H), 6.91 (t, [M + H]+ J = 7.5 Hz, 1H), 6.79 (d, J = 8.1Hz, 1H), 5.28-5.18 (m, 1H), 4.32-4.18 (m, 2H), 3.08 (s, 6H), 2.19 (dd, J= 9.0, 4.8 Hz, 1H), 2.09-2.00 (m, 1H). 172 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.07 (Method (d, J = 7.4 Hz, 1H), 8.53 (d, J = 1.2 Hz, L2):Rt = 1H), 8.31 (dd, J = 9.5, 6.3 Hz, 1H), 3.05 min; 7.64-7.56 (m, 2H),7.47-7.38 (m, 1H), m/z = 494 7.38-7.29 (m, 2H), 7.19-7.12 (m, 1H), [M +H]+ 6.94-6.86 (m, 1H), 6.81-6.75 (m, 1H), 5.22 (q, J = 6.8, 6.3 Hz, 1H),4.31-4.18 (m, 2H), 3.07 (s, 6H), 2.24-2.13 (m, 1H), 2.07-1.98 (m, 1H).173 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.91 (s, 1H), 7.75(dd, J = 9.9, 2.9 Hz, L2): Rt = 1H), 7.52-7.44 (m, 2H), 7.36-7.18 (m,3.40 min; 4H), 7.11 (d, J = 7.4 Hz, 1H), 6.93 (td, m/z = 478 J = 7.5,1.1 Hz, 1H), 6.87 (dd, J = 8.3, [M + H]+ 1.0 Hz, 1H), 5.40-5.33 (m, 1H),4.39- 4.31 (m, 1H), 4.23-4.15 (m, 1H), 3.10 (s, 6H), 2.44-2.35 (m, 1H),2.25-2.17 (m, 1H). 174 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method8.93 (s, 1H), 7.75 (dd, J = 9.9, 2.9 Hz, L2): Rt = 1H), 7.62-7.59 (m,1H), 7.52-7.46 3.46 min; (m, 2H), 7.44-7.39 (m, 2H), 7.30 (d, m/z = 476J = 7.7 Hz, 1H), 7.24-7.18 (m, 1H), [M + H]+ 7.12 (d, J = 7.5 Hz, 1H),6.93 (td, J = 7.5, 1.2 Hz, 1H), 6.87 (dd, J = 8.3, 1.0 Hz, 1H),5.41-5.34 (m, 1H), 4.39-4.31 (m, 1H), 4.23-4.16 (m, 1H), 3.10 (s, 6H),2.44-2.35 (m, 1H), 2.25-2.17 (m, 1H). 175 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.88 (s, 1H), 7.81 (dd, J = 10.0, 2.9 Hz, L2):Rt = 1H), 7.51-7.45 (m, 2H), 7.34-7.27 3.59 min; (m, 2H), 7.23-7.17 (m,2H), 7.04 (d, m/z = 494 J = 7.6 Hz, 1H), 6.92 (td, J = 7.5, 1.2 [M + H]+Hz, 1H), 6.86 (dd, J = 8.2, 1.1 Hz, 1H), 5.40-5.33 (m, 1H), 4.38-4.31(m, 1H), 4.22-4.15 (m, 1H), 3.11 (s, 6H), 2.43- 2.34 (m, 1H), 2.24-2.16(m, 1H). 176 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.86 (s,1H), 7.82 (dd, J = 10.0, 2.9 Hz, L2): Rt = 1H), 7.42 (dd, J = 8.3, 2.9Hz, 1H), 3.40 min; 7.37-7.30 (m, 1H), 7.29-7.12 (m, 4H), m/z = 494 7.02(s, 1H), 6.91 (td, J = 7.5, 1.1 Hz, [M + H]+ 1H), 6.85 (dd, J = 8.3, 1.0Hz, 1H), 5.40-5.32 (m, 1H), 4.37-4.30 (m, 1H), 44.2-2.14 (m, 1H), 3.12(s, 6H), 2.42- 2.33 (m, 1H), 2.23-2.15 (m, 1H). 177 LC-MS ¹H-NMR (400MHz, Chloroform-d) δ (Method 8.91 (s, 1H), 7.78 (dd, J = 9.9, 2.9 Hz,L2): Rt = 1H), 7.48 (dd, J = 8.6, 2.9 Hz, 1H), 3.51 min; 7.30 (d, J =7.7 Hz, 1H), 7.24-7.13 (m, m/z = 478 3H), 7.04 (d, J = 7.4 Hz, 1H), 6.94(td, [M + H]+ J = 7.5, 1.2 Hz, 1H), 6.91-6.84 (m, 2H), 5.41-5.34 (m,1H), 4.39-4.32 (m, 1H), 4.24-4.16 (m, 1H), 3.11 (s, 6H), 2.44-2.35 (m,1H), 2.25-2.17 (m, 1H). 178 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.90 (s, 1H), 7.77 (dd, J = 9.9, 2.9 Hz, L2): Rt = 1H), 7.47(dd, J = 8.6, 2.9 Hz, 1H), 3.73 min; 7.40 (s, 1H), 7.32-7.24 (m, 2H),7.24- m/z = 494 7.18 (m, 1H), 7.15 (dt, J = 8.4, 2.1 Hz, [M + H]+ 1H),7.05 (d, J = 7.5 Hz, 1H), 6.93 (td, J = 7.5, 1.1 Hz, 1H), 6.86 (dd, J =8.3, 0.9 Hz, 1H), 5.40-5.33 (m, 1H), 4.38- 4.31 (m, 1H), 4.23-4.16 (m,1H), 3.10 (s, 6H), 2.44-2.34 (m, 1H), 2.25-2.16 (m, 1H). 179 LC-MS¹H-NMR (400 MHz, Chlofoform-d) δ (Method 8.88 (s, 1H), 7.80 (dd, J =10.0, 2.9 Hz, L2): Rt = 1H), 7.48 (dd, J = 8.3, 2.8 Hz, 1H), 3.63 min;7.44-7.35 (m, 2H), 7.28 (d, J = 7.8 Hz, m/z = 494 1H), 7.23-7.17 (m,1H), 7.13 (t, J = 8.9 [M + H]+ Hz, 1H), 7.04 (d, J = 7.4 Hz, 1H), 6.92(td, J = 7.5, 1.1 Hz, 1H), 6.86 (dd, J = 8.3, 1.0 Hz, 1H), 5.39-5.33 (m,1H), 4.38-4.30 (m, 1H), 4.22-4.14 (m, 1H), 3.11 (s, 6H), 2.43-2.34 (m,1H), 2.24-2.16 (m, 1H). 180 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.87 (s, 1H), 7.81 (dd, J = 10.0, 2.9 Hz, L2): Rt = 1H), 7.41(dd, J = 8.3, 2.9 Hz, 1H), 3.34 min; 7.34-7.26 (m, 3H), 7.23-7.18 (m,1H), m/z = 494 7.12-7.00 (m, 2H), 6.92 (td, J = 7.5, [M + H]+ 1.2 Hz,1H), 6.86 (dd, J = 8.3, 1.1 Hz, 1H), 5.40-5.33 (m, 1H), 4.38-4.30 (m,1H), 4.22-4.14 (m, 1H), 3.12 (s, 6H), 2.43-2.34 (m, 1H), 2.24-2.15 (m,1H). 181 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]: −0.008 (2.14),0.008 (1.84), L1): Rt = 1.356 (0.66), 2.056 (0.64), 2.064 (0.68), 1.37min; 2.075 (0.73), 2.091 (1.03), 2.099 (0.87), MS 2.106 (0.63), 2.192(0.43), 2.201 (0.68), (ESIpos): 2.213 (0.94), 2.225 (0.91), 2.235(0.85), m/z = 550 2.247 (0.57), 2.255 (0.46), 2.523 (1.40), [M + H]+2.899 (3.69), 3.449 (0.46), 3.461 (0.72), 3.480 (2.72), 3.492 (5.13),3.504 (4.92), 3.515 (2.44), 3.535 (0.65), 4.230 (0.50), 4.251 (1.50),4.259 (1.25), 4.272 (2.17), 4.281 (2.06), 4.298 (1.28), 4.317 (0.47),5.241 (0.65), 5.255 (1.41), 5.274 (1.39), 5.288 (0.61), 6.792 (2.63),6.810 (2.75), 6.812 (2.85), 6.918 (1.30), 6.921 (1.35), 6.937 (2.66),6.939 (2.66), 6.955 (1.62), 6.958 (1.57), 7.156 (1.35), 7.160 (1.44),7.177 (2.18), 7.194 (1.07), 7.198 (1.05), 7.389 (2.31), 7.407 (2.12),7.632 (5.83), 7.636 (16.00), 7.638 (8.92), 7.689 (1.90), 7.707 (2.69),7.710 (2.47), 7.728 (2.42), 7.832 (3.00), 7.835 (3.26), 7.850 (2.42),7.853 (2.35), 8.260 (2.52), 8.263 (2.63), 8.281 (2.36), 8.284 (2.26),8.718 (9.84), 9.157 (2.51), 9.177 (2.41). 182 3.3 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ (Method [ppm]: −0.008 (0.74), 0.008 (0.62), L1): Rt = 1.407(16.00), 2.086 (0.51), 2.523 (0.47), 1.08 min; 4.258 (0.40), 4.268(1.03), 4.283 (0.99), MS 4.289 (0.91), 4.297 (0.51), 4.305 (0.58),(ESIpos): 6.787 (0.59), 6.806 (0.68), 6.893 (0.65), m/z = 578 7.167(0.52), 7.328 (0.53), 7.347 (0.50), [M + H]+ 7.578 (0.54), 7.599 (0.48),7.611 (0.71), 7.615 (0.79), 7.626 (2.75), 7.631 (1.63), 7.769 (0.69),7.787 (0.59), 8.210 (0.42), 8.334 (0.53), 8.355 (0.50), 8.579 (1.74),9.051 (0.51), 9.072 (0.50). 183 6 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ(Method [ppm]: 1.431 (16.00), 3.042 (4.04), L1): Rt = 3.948 (2.03),4.284 (0.56), 6.792 (0.61), 1.49 min; 6.811 (0.68), 6.911 (0.63), 7.173(0.49), MS 7.354 (0.52), 7.373 (0.48), 7.644 (7.05), (ESIpos): 7.683(0.45), 7.701 (0.62), 7.722 (0.55), m/z = 592 7.837 (0.68), 7.840(0.68), 7.855 (0.56), [M + H]+ 7.858 (0.51), 8.350 (0.60), 8.353 (0.58),8.371 (0.56), 8.374 (0.52), 8.763 (2.16), 9.234 (0.57), 9.254 (0.55).184 3 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]: 0.008 (1.32),0.912 (7.39), 0.931 L1): Rt = (16.00), 0.949 (7.79), 1.634 (0.73), 0.95min; 1.652 (2.85), 1.670 (5.25), 1.688 (5.08), MS 1.706 (2.51), 1.725(0.52), 2.008 (0.45), (ESIpos): 2.024 (0.86), 2.033 (1.06), 2.042(1.11), m/z = 506 2.058 (1.52), 2.068 (1.52), 2.086 (3.21), [M + H]+2.126 (0.70), 2.138 (1.27), 2.155 (1.51), 2.167 (1.10), 2.178 (0.76),2.328 (0.44), 2.523 (2.24), 2.670 (0.48), 3.451 (1.52), 3.468 (3.30),3.476 (3.00), 3.482 (2.99), 3.489 (3.03), 3.506 (1.25), 4.235 (0.77),4.253 (2.65), 4.268 (4.11), 4.278 (3.48), 4.286 (2.21), 4.306 (0.49),5.236 (1.01), 5.251 (2.08), 5.269 (1.99), 5.284 (0.85), 5.754 (0.58),6.782 (3.55), 6.803 (3.93), 6.880 (1.99), 6.899 (3.97), 6.917 (2.28),7.141 (1.96), 7.145 (1.96), 7.162 (3.10), 7.180 (1.49), 7.287 (3.39),7.305 (3.06), 7.516 (2.25), 7.535 (3.39), 7.555 (2.58), 7.600 (3.94),7.605 (3.48), 7.621 (14.17, 7.626 (9.44), 7.732 (4.27), 7.750 (3.54),7.951 (2.25), 8.412 (3.35), 8.433 (3.11), 8.535 (9.75), 8.986 (3.00),9.006 (2.85). 185 2 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]:1.108 (4.30), 1.783 (2.07), 1.917 L1): Rt = (2.11), 1.930 (1.65), 2.075(1.64), 2.086 0.72 min; (5.94), 2.156 (1.41), 2.171 (1.60), 2.185 MS(1.08), 2.328 (0.70), 2.366 (0.42), 2.670 (ESIneg): (0.85), 2.709(0.44), 2.752 (4.01), 2.770 m/z = 505 (0.64), 2.789 (0.58), 2.994(3.16), 3.009 [M − H]− (6.19), 3.024 (3.45), 3.168 (0.68), 3.417 (1.38),3.527 (1.42), 3.731 (1.06), 4.266 (4.94), 5.247, (2.07), 5.260 (1.94),5.754 (8.83), 6.786 (3.64), 6.806 (4.14), 6.897 (1.83), 6.916 (3.84),6.934 (2.23), 7.150 (1.96), 7.167 (3.21), 7.186 (1.56), 7.323 (3.41),7.341 (3.12), 7.540 (2.24), 7.559 (3.64), 7.579 (2.41), 7.611 (7.22),7.617 (16.00), 7.746 (4.79), 7.763 (4.88), 8.346 (1.16), 8.400 (0.60),8.421 (3.41), 8.442 (3.22), 8.513 (7.91), 8.538 (1.10), 9.052 9 (1.55),9.069 (1.55). 186 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (0.48), 0.008 (3.60), 0.146 (0.48), L1): Rt = 1.140 (6.02), 1.235(0.55), 1.889 (1.18), 0.80 min; 2.031 (2.12), 2.051 (2.52), 2.063(2.18), MS 2.073 (1.69), 2.116 (2.61), 2.156 (1.44), (ESIpos): 2.170(1.66), 2.186 (0.98), 2.206 (0.83), m/z = 534 2.327 (1.00), 2.366(0.43), 2.669 (1.05), [M + H]+ 2.710 (0.52), 3.475 (2.09), 3.503 (2.40),3.737 (1.58), 3.759 (1.14), 3.813 (0.91), 3.835 (1.75), 3.865 (2.04),3.877 (2.60), 3.892 (1.74), 3.903 (1.61), 4.254 (3.26), 4.266 (5.15),4.280 (3.06), 4.366 (2.18), 4.538 (0.55), 5.032 (2.78), 5.207 (0.85),5.221 (1.83), 5.241 (1.89), 5.255 (0.85), 6.781 (3.54), 6.801 (4.00),6.891 (1.71), 6.910 (3.70), 6.929 (2.12), 7.145 (1.81), 7.162 (2.90),7.183 (1.41), 7.305 (3.14), 7.324 (2.84), 7.464 (2.18), 7.482 (3.14),7.503 (2.58), 7.606 (4.72), 7.610 (4.81), 7.621 (16.00), 7.625 (9.59),7.706 (3.90), 7.724 (3.35), 8.133 (13.65,) 8.279 (3.24), 8.299 (3.04),8.434 (10.50), 9.044 (3.03), 9.065 (2.98), 12.729 (0.68). 187 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.83), −0.008 (7.47),0.008 L1): Rt = (6.76), 0.146 (0.89), 1.235 (0.41), 1.260 0.80 min;(2.01), 1.335 (2.31), 1.901 (1.24), 2.005 MS (1.48), 2.017 (2.25), 2.028(2.37), 2.040 (ESIpos): (2.49), 2.049 (2.61), 2.085 (0.53), 2.149 m/z =534 (1.42), 2.167 (1.24), 2.185 (1.19), 2.200 [M + H]+ (0.89), 2.327(1.36), 2.366 (0.83), 2.523 (4.80), 2.670 (1.60), 2.710 (1.07), 3.501(1.84), 3.527 (2.07), 3.732 (1.54), 3.780 (1.01), 3.800 (1.78), 3.821(1.54), 3.852 (1.72), 3.862 (1.78), 3.879 (1.54), 3.889 (1.42), 4.258(5.39), 4.270 (3.32), 4.374 (2.31), 5.029 (3.67), 5.037 (3.61), 5.197(0.89), 5.212 (2.01), 5.231 (2.07), 5.246 (0.95), 5.753 (8.18), 6.782(3.61), 6.803 (4.09), 6.895 (1.84), 6.913 (3.97), 6.932 (2.31), 7.147(1.96), 7.165 (3.20), 7.182 (1.60), 7.310 (3.38), 7.328 (3.08), 7.463(1.72), 7.483 (2.79), 7.503 (2.13), 7.609 (3.08), 7.621 (16.00), 7.625(9.84), 7.709 (3.67), 7.725 (3.20), 8.132 (2.01), 8.276 (3.08), 8.297(2.90), 8.428 (6.76), 9.044 (2.37), 9.065 (2.37), 12.724 (0.71). 188 4.5LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.51), 0.008(2.40), 1.778 (0.76), L1): Rt = 1.789 (0.83), 1.806 (1.00), 1.999(0.94), 1.18 min; 2.012 (0.94), 2.020 (0.92), 2.034 (0.71), MS 2.327(0.91), 2.670 (1.00), 4.034 (0.75), (ESIneg): 4.055 (1.64), 4.076(1.16), 4.161 (1.16), m/z = 514 4.171 (1.05), 4.179 (1.30), 4.198(0.76), [M − H]− 5.017 (0.70), 5.031 (1.46), 5.050 (1.46), 5.065 (0.67),5.754 (0.43), 6.746 (2.94), 6.766 (3.26), 6.848 (1.33), 6.868 (2.92),6.885 (1.86), 7.049 (2.67), 7.066 (2.16), 7.127 (1.46), 7.148 (2.40),7.165 (1.19), 7.419 (2.81), 7.438 (3.05), 7.721 (4.19), 7.724 (6.58),7.730 (16.00), 7.734 (7.25), 7.816 (2.30), 7.835 (3.08), 7.856 (2.38),8.049 (3.13), 8.052 (3.29), 8.067 (2.75), 8.136 (6.83), 8.138 (6.75),8.649 (6.74), 8.652 (6.63), 9.105 (2.64), 9.125 (2.56), 9.233 (10.60).189 5 LC-MS 1H-NMR (400 MHz, DMSO-d6) δ (Method [ppm] = 9.12-9.22 (m,2H), 8.35 (s, 2H), L1): Rt = 8.03 (dd, 1H), 7.88-7.96 (m, 1H), 1.27 min;7.79-7.88 (m, 1H), 7.67-7.76 (m, 2H), MS 7.25 (d, 1H), 7.11-7.20 (m,1H), (ESIpos): 6.88-6.97 (m, 1H), 6.76 (d, 1H), m/z = 534 5.01-5.13 (m,1H), 4.07-4.28 (m, 2H), [M + H]+ 2.02-2.15 (m, 1H), 1.94 (dtd, 1H). 190LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (1.34), 0.008(11.80), 0.146 L1): Rt = (1.34), 1.234 (0.47), 2.050 (1.17), 2.058 1.11min; (1.31), 2.072 (1.34), 2.085 (1.95), 2.210 MS (1.70), 2.222 (1.64),2.231 (1.56), 2.245 (ESIpos): (1.09), 2.327 (1.39), 2.366 (0.75), 2.523m/z = 518 (4.79), 2.669 (1.47), 2.710 (0.78), 3.060 [M + H]+ (0.45),3.162 (0.56), 3.174 (0.58), 3.249 (1.59), 3.269 (5.20), 3.280 (11.55),3.291 (13.72), 3.864 (8.68), 3.875 (14.11), 3.886 (8.04), 4.223 (0.95),4.244 (2.73), 4.252 (2.17), 4.265 (3.56), 4.293 (2.25), 4.312 (0.81),5.245 (1.11), 5.259 (2.50), 5.277 (2.50), 5.292 (1.09), 5.754 (0.53),6.788 (4.59), 6.809 (5.04), 6.917 (2.25), 6.933 (4.79), 6.952 (2.87),7.157 (2.56), 7.175 (4.03), 7.192 (1.98), 7.377 (4.26), 7.395 (4.01),7.484 (3.14), 7.506 (6.04), 7.528 (4.70), 7.586 (2.67), 7.591 (2.98),7.598 (2.95), 7.603 (3.09), 7.612 (2.11), 7.619 (1.89), 7.625 (1.92),7.673 (3.28), 7.691 (4.84), 7.712 (4.31), 7.796 (8.77), 7.815 (7.35),8.253 (4.51), 8.256 (4.54), 8.274 (4.20), 8.419 (0.42), 8.679 (16.00),9.157 (4.45), 9.177 (4.29). 191 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 3.284 (1.86), 3.296 (2.09), 3.310 (16.00), L1): Rt = 3.864(1.44), 3.875 (2.23), 3.886 (1.28), 1.14 min; 4.236 (0.43), 4.260(0.54), 5.248 (0.41), MS 6.782 (0.73), 6.802 (0.80), 6.924 (0.74),(ESIpos): 6.941 (0.43), 7.168 (0.63), 7.364 (0.68), m/z = 536 7.383(0.61), 7.593 (0.46), 7.617 (0.89), [M + H]+ 7.641 (0.45), 7.675 (0.47),7.688 (0.55), 7.695 (0.75), 7.706 (0.80), 7.714 (0.54), 7.726 (0.64),7.774 (0.85), 7.790 (0.54), 8.295 (0.68), 8.313 (0.62), 8.626 (2.30),9.156 (0.68), 9.176 (0.65). 192 LC-MS ¹H-NMR (400 MHz DMSO-d6) δ [ppm]:(Method −0.008 (0.73), 0.008 (0.67), 1.038 (0.70), L1): Rt = 1.056(1.42), 1.073 (0.73), 1.356 (16.00), 1.25 min; 2.069 (0.41), 2.183(2.23), 2.198 (0.40), MS 2.523 (0.65), 3.162 (5.24), 3.175 (5.43),(ESIpos): 3.261 (1.01), 3.272 (2.30), 3.284 (2.43), m/z = 552 3.295(1.34), 3.862 (1.80), 3.873 (3.10), [M + H]+ 3.884 (1.73), 4.062 (0.46),4.075 (1.30), 4.088 (1.26), 4.101 (0.43), 4.231 (0.62), 4.238 (0.48),4.252 (0.64), 4.259 (0.79), 4.267 (0.64), 4.274 (0.50), 4.283 (0.53),4.335 (0.42), 5.238 (0.57), 5.257 (0.58), 6.631 (0.75), 6.784 (1.09),6.802 (1.21), 6.870 (1.34), 6.902 (0.56), 6.905 (0.54), 6.921 (1.16),6.939 (0.71), 6.942 (0.64), 7.148 (0.56), 7.152 (0.59), 7.169 (0.92),7.187 (0.45), 7.190 (0.45), 7.362 (0.95), 7.381 (0.90), 7.502 (2.90),7.506 (3.06), 7.636 (0.78), 7.659 (1.54), 7.682 (0.86), 7.688 (1.02),7.693 (1.74), 7.698 (0.87), 8.319 (0.77), 8.334 (0.82), 8.342 (0.81),8.358 (0.73), 8.680 (4.09), 9.152 (1.05), 9.172 (1.01). 193 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.61 −0.008 (8.00), 0.008L6): Rt = (5.20), 0.146 (0.61), 1.903 (1.83), 2.018 1.46 min; (3.13),2.029 (3.53), 2.040 (3.33), 2.050 MS (3.82), 2.156 (2.07), 2.170 (2.36),2.185 (ESIpos): (1.71), 2.327 (2.03), 2.366 (1.50), 2.518 m/z = 552(10.92), 2.523 (9.71), 2.669 (2.07), 2.710 [M + H]+ (1.58), 3.472(1.54), 3.499 (2.56), 3.523 (1.34), 3.736 (2.19), 3.833 (1.71), 3.863(2.48), 3.876 (2.52), 3.892 (1.83), 4.257 (5.69), 4.266 (6.05), 4.370(3.09), 5.029 (4.51), 5.220 (2.48), 5.754 (1.38), 6.783 (4.95), 6.802(5.28), 6.894 (2.88), 6.913 (5.20), 6.931 (3.01), 7.146 (2.80), 7.164(4.35), 7.184 (1.99), 7.307 (4.39), 7.326 (3.78), 7.461 (2.19), 7.480(3.49), 7.500 (2.36), 7.721 (4.75), 7.739 (4.06), 7.789 (16.00), 7.805(15.51), 8.275 (3.57), 8.297 (3.25), 8.439 (5.32), 9.042 (3.25), 9.063(3.09). 194 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.150(0.76), 1243 (1.14), 1.862 (2.65), L6): Rt = 1.904 (3.87), 2.034 (6.99),2.142 (4.04), 1.37 min; 2.157 (4.55), 2.327 (2.86), 2.365 (1.05), MS2.668 (3.16), 2.689 (9.05), 2.709 (1.60), (ESIpos): 2.889 (0.97), 3.508(3.16), 3.741 (3.75), m/z = 534 3.873 (5.09), 4.249 (14.53), 4.384(6.23), [M + H]+ 5.049 (4.97), 5.203 (5.26), 5.754 (16.00), 6.770(9.35), 6.791 (10.32), 6.876 (5.64), 6.895 (11.49), (6.912), (6.48),7.135 (5.73), 7.153 (8.80), 7.172 (4.63), 7.286 (10.78), 7.305 (12.25),7.422 (4.88), 7.494 (4.88), 7.537 (6.19), 7.663 (5.05), 8.133 (2.95),8.331 (10.27), 9.031 (3.83). 195 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.149 (1.44), −0.008 (12.33), 0.008 L1): Rt = (10.95),0.146 (1.32), 1.258 (0.72), 1.902 0.75 min; (4.39), 2.034 (9.32), 2.148(5.11), 2.164 MS (5.71), 2.180 (4.39), 2.197 (3.67), 2.327 (ESIpos):(4.99), 2.366 (2.71), 2.523 (12.27), 2.670 m/z = 536 (4.75), 2.689(1.26), 2.709 (1.98), 2.812 [M + H]+ (0.78), 3.509 (4.03), 3.745 (4.09),3.874 (7.82), 4.257 (16.00), 4.376 (6.92), 5.037 (7.10), 5.221 (6.32),5.754 (14.80), 6.777 (11.31), 6.797 (12.27), 6.882 (7.64), 6.901(15.28), 6.919 (8.84), 7.142 (6.86), 7.159 (10.83), 7.178 (5.23), 7.292(12.75), 7.311 (11.49), 7.493 (5.29), 7.585 (5.23), 7.664 (9.26), 8.132(2.05), 8.320 (6.26), 8.361 (10.23), 9.030 (4.45). 196 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm] (Method −0.149 (0.87), 1.913 (2.01), 2.048 (3.88),L1): Rt = 2.170 (2.51), 2.327 (1.94), 2.523 (5.82), 0.74 min; 2.669(1.97), 3.516 (1.51), 3.868 (2.41), MS 4.265 (7.06), 4.377 (3.51), 5.044(3.01), (ESIpos): 5.223 (2.74), 5.754 (16.00), 6.784 (6.46), m/z = 5186.803 (6.93), 6.892 (3.08), 6.910 (6.43), [M + H]+ 6.928 (3.88), 7.147(3.25), 7.164 (5.12), 7.183 (2.68), 7.301 (4.92), 7.320 (4.62), 7.492(5.12), 7.567 (3.68), 7.579 (3.75), 7.684 (3.48), 7.701 (3.18), 7.779(5.82), 7.784 (5.72), 7.798 (5.82), 7.803 (5.62), 8.131 (2.91), 8.260(2.74), 8.409 (3.45), 9.059 (1.97). 197 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method 0.008 (0.53), 2.055 (0.47), 2.182 (0.43), L1): Rt =2.194 (0.43), 2.523 (1.20), 3.072 (16.00), 0.93 min; 4.234 (0.76), 4.241(0.67), 4.253 (1.11), MS 4.261 (1.14), 4.276 (0.61), 5.233 (0.66),(ESIpos): 5.253 (0.62), 5.754 (0.79), 6.781 (1.22), m/z = 494 6.799(1.31), 6.895 (0.67), 6.914 (1.23), [M + H]+ 6.933 (0.72), 7.147 (0.66),7.164 (0.99), 7.182 (0.48), 7.342 (1.07), 7.361 (0.96), 7.586 (0.87),7.609 (1.65), 7.634 (1.59), 7.652 (1.37), 7.668 (1.04), 7.673 (1.40),7.687 (1.16), 7.707 (0.85), 7.733 (1.36), 7.747 (0.90), 8.252 (1.19),8.256 (1.15), 8.273 (1.10), 8.558 (4.01), 9.072 (1.07), 9.092 (0.99).198 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]: −0.008 (2.98),0.008 (2.20), L1): Rt = 1.031 (16.00), 1.046 (15.86), 2.114 1.17 min;(0.42), 2.123 (0.49), 2.130 (0.48), 2.180 MS (0.43), 2.207 (0.73), 2.231(0.54), 2.290 (ESIpos): (0.86), 2.524 (0.71), 2.599 (7.81), 2.716 m/z =506 (2.57), 2.767 (1.36), 2.782 (4.28), 3.063 [M + H]+ (13.77), 3.096(5.64), 3.118 (5.22), 3.128 (2.34), 3.758 (0.72), 3.774 (0.93), 3.789(0.67), 4.223 (0.45), 4.234 (0.63), 4.240 (0.73), 4.263 (1.22), 4.268(1.11), 4.291 (0.83), 4.347 (0.83), 4.356 (1.15), 4.374 (0.55), 4.384(0.64), 6.029 (0.51), 6.045 (0.60), 6.054 (0.62), 6.070 (0.47), 6.750(0.57), 6.770 (0.61), 6.816 (1.14), 6.836 (1.59), 6.854 (0.46), 6.942(0.62), 6.952 (0.92), 6.970 (1.59), 6.989 (0.90), 7.088 (0.43), 7.162(1.02), 7.181 (1.47), 7.200 (0.67), 7.303 (1.07), 7.322 (0.94), 7.359(0.50), 7.378 (0.44), 7.584 (1.50), 7.588 (2.38), 7.600 (0.65), 7.604(0.60), 7.623 (0.60), 7.641 (2.51), 7.645 (2.60), 7.653 (1.17), 7.674(6.23), 7.678 (4.23), 7.684 (1.61), 7.760 (0.60), 7.763 (0.61), 7.778(0.49), 7.781 (0.49), 7.810 (1.91), 7.828 (1.43), 8.233 (1.73), 8.252(1.81), 8.270 (0.45), 8.621 (1.03), 8.626 (0.75), 8.649 (1.42), 8.685(3.00). 199 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 1.524(0.76), 1.830 (0.77), 1.842 (0.85), L1): Rt = 2.669 (0.44), 3.368(16.00), 3.946 (0.56), 1.47 min; 3.970 (1.28), 3.993 (1.00), 4.034(1.18), MS 4.049 (1.17), 4.939 (1.39), 4.958 (1.38), (ESIpos): 5.753(0.43), 6.593 (3.28), 6.613 (3.44), m/z = 554 6.720 (2.29), 6.740(2.71), 6.751 (1.49), [M + H]+ 6.769 (2.88), 6.792 (2.81), 6.811 (1.48),6.997 (1.58), 7.015 (1.39), 7.099 (1.40), 7.123 (3.83), 7.142 (4.69),7.163 (2.24), 7.676 (2.67), 7.680 (2.28), 7.686 (2.02), 7.707 (3.17),7.716 (8.16), 7.721 (7.33), 7.909 (2.73), 7.925 (2.29), 7.963 (2.59),7.984 (2.17), 8.892 (2.25), 8.912 (2.12), 8.993 (6.13). 200 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.45), −0.008 (4.14), 0.008L1): Rt = (3.74), 0.146 (0.49), 1.157 (4.28), 1.175 1.14 min; (8.62),1.192 (4.37), 1.237 (1.13), 1.398 MS (6.32), 1.988 (16.00), 2.019(1.27), 2.040 (ESIpos): (1.53), 2.054 (1.76), 2.073 (1.64), 2.191 m/z =552 (1.72), 2.204 (1.64), 2.213 (1.69), 2.227 [M + H]+ (1.15), 2.327(1.34), 2.366 (0.92), 2.522 (4.51), 2.669 (1.41), 2.710 (0.92), 3.247(1.22), 3.265 (2.51), 3.295 (9.16), 3.874 (12.08), 4.002 (1.25), 4.020(3.83), 4.038 (3.76), 4.056 (1.29), 4.200 (0.85), 4.224 (2.40), 4.249(3.43), 4.258 (2.82), 4.275 (2.47), 5.230 (2.35), 5.245 (2.44), 5.754(7.50), 6.774 (5.36), 6.795 (5.92), 6.887 (2.61), 6.905 (5.47), 6.924(3.27), 7.142 (2.89), 7.159 (4.46), 7.177 (2.21), 7.181 (2.21), 7.344(6.79), 7.360 (6.16), 7.363 (7.33), 7.370 (3.55), 7.374 (2.84), 7.389(3.59), 7.393 (3.43), 7.452 (2.96), 7.466 (3.38), 7.472 (4.89), 7.485(5.24), 7.491 (2.68), 7.505 (2.61), 7.646 (3.76), 7.669 (6.51), 7.691(3.88), 7.734 (6.13), 7.737 (6.30), 7.754 (5.36), 7.757 (5.12), 8.341(3.74), 8.356 (3.99), 8.364 (3.95), 8.380 (3.64), 8.604 (9.75), 8.612(10.24), 9.143 (2.98), 9.149 (3.15), 9.163 (2.98), 9.170 (2.96). 201LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.72), 0.008(2.48), 2.030 (0.56), L1): Rt = 2.039 (0.58), 2.051 (0.60), 2.066(0.88), 1.08 min; 2.073 (0.77), 2.086 (3.11), 2.181 (0.62), MS 2.193(0.79), 2.205 (0.79), 2.215 (0.72), (ESIpos): 2.227 (0.47), 2.327(0.60), 2.332 (0.43), m/z = 554 2.523 (1.88), 2.559 (1.25), 2.578(1.51), [M + H]+ 2.596 (1.97), 2.614 (1.49), 2.634 (0.95), 2.651 (0.54),2.665 (0.50), 2.669 (0.65), 2.674 (0.47), 3.710 (1.27), 3.720 (1.53),3.728 (2.20), 3.737 (2.18), 3.744 (1.48), 3.755 (1.21), 3.845 (1.98),3.877 (3.98), 3.909 (1.91), 4.223 (0.41), 4.244 (1.29), 4.252 (1.09),4.264 (1.96), 4.272 (2.19), 4.287 (1.15), 4.306 (0.42), 5.237 (0.54),5.251 (1.20), 5.271 (1.20), 5.285 (0.52), 5.754 (4.52), 6.792 (2.31),6.810 (2.55), 6.812 (2.55), 6.904 (1.13), 6.907 (1.12), 6.923 (2.38),6.942 (1.43), 6.944 (1.35), 7.156 (1.18), 7.160 (1.25), 7.177 (1.91),7.195 (0.96), 7.199 (0.91), 7.355 (1.97), 7.373 (1.85), 7.638 (16.00),7.657 (0.42), 7.664 (1.80), 7.682 (2.37), 7.685 (2.13), 7.703 (2.16),7.834 (2.60), 7.837 (2.71), 7.852 (2.23), 7.855 (2.07), 8.237 (2.33),8.240 (2.34), 8.258 (2.24), 8.261 (2.06), 8.688 (8.85), 9.217 (2.14),9.237 (2.09). 202 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (0.84), −0.008 (8.37), 0.008 L1): Rt = (8.34), 0.146 (0.90),0.994 (0.52), 1.236 1.04 min; (1.34), 1.336 (0.57), 1.782 (1.25), 1.916MS (1.25), 2.327 (1.74), 2.366 (1.09), 2.670 (ESIpos): (1.88), 2.710(1.09), 2.765 (2.18), 2.781 m/z = 533 (4.28), 2.797 (2.15), 3.963(0.87), 3.984 [M + H]+ (2.07), 4.006 (1.34), 4.111 (1.55), 4.873 (1.80),4.888 (3.60), 4.905 (2.43), 4.921 (1.58), 4.936 (1.88), 4.953 (1.31),6.688 (3.46), 6.709 (3.87), 6.716 (1.80), 6.735 (3.46), 6.754 (2.51),6.856 (3.41), 6.875 (2.53), 7.058 (1.66), 7.079 (2.70), 7.097 (1.53),7.614 (11.50), 7.618 (16.00), 7.636 (4.99), 7.641 (5.42), 7.657 (1.20),7.680 (1.61), 7.743 (1.77), 7.761 (4.12), 7.781 (3.76), 7.798 (4.58),7.812 (2.21), 8.383 (2.67), 8.403 (2.70), 8.563 (2.67), 8.580 (2.43),8.662 (0.57), 9.033 (11.99), 11.367 (0.60). 203 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 0.008 (2.46), 2.064 (0.79), 2.071 (0.81), L4):Rt = 2.084 (0.92), 2.099 (1.21), 2.206 (0.83), 3.85 min; 2.218 (1.14),2.230 (1.08), 2.240 (1.07), MS 2.252 (0.73), 2.327 (0.63), 2.522 (1.85),(ESIpos): 2.669 (0.67), 3.484 (3.25), 3.654 (5.30), m/z = 582 3.666(4.89), 4.223 (0.66), 4.244 (1.80), [M + H]+ 4.251 (1.36), 4.265 (1.77),4.272 (2.23), 4.282 (1.77), 4.297 (1.50), 4.316 (0.61), 5.240 (0.78),5.254 (1.76), 5.273 (1.72), 5.287 (0.74), 5.754 (1.31), 6.794 (3.28),6.814 (3.60), 6.920 (1.57), 6.937 (3.30), 6.955 (1.94), 7.160 (1.66),7.163 (1.71), 7.181 (2.72), 7.198 (1.33), 7.392 (2.85), 7.409 (2.68),7.635 (8.69), 7.639 (16.00), 7.647 (5.36), 7.652 (4.23), 7.707 (2.28),7.725 (3.22), 7.746 (2.80), 7.872 (3.73), 7.887 (2.92), 8.399 (3.12),8.417 (2.89), 8.770 (11.57), 9.239 (3.04), 9.260 (2.96). 204 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.150 (1.38), −0.008(13.30), 0.008 L1): Rt = (13.66), 0.146 (1.50), 1.235 (1.56), 2.049 0.83min; (1.20), 2.076 (1.68), 2.206 (1.50), 2.217 MS (1.62), 2.226 (1.44),2.322 (2.70), 2.327 (ESIpos): (3.60), 2.331 (2.70), 2.366 (2.52), 2.522m/z = 508 (13.90), 2.664 (3.00), 2.669 (3.84), 2.674 [M + H]+ (2.88),2.709 (2.46), 3.218 (3.96), 3.241 (9.11), 3.262 (8.45), 3.273 (10.25),3.285 (11.63), 3.858 (7.85), 3.870 (13.30), 3.881 (7.43), 4.223 (0.72),4.243 (2.64), 4.251 (2.10), 4.264 (3.90), 4.273 (3.96), 4.289 (2.16),4.381 (4.85), 4.403 (9.65), 4.425 (4.67), 5.240 (1.02), 5.255 (2.40),5.275 (2.34), 5.288 (0.96), 5.753 (2.76), 6.784 (4.43), 6.802 (4.91),6.871 (3.66), 6.890 (7.49), 6.909 (5.87), 6.923 (4.73), 6.942 (2.82),7.109 (4.55), 7.127 (3.90), 7.151 (2.46), 7.168 (3.78), 7.186 (1.92),7.237 (4.19), 7.256 (3.78), 7.363 (4.01), 7.382 (3.72), 7.618 (2.64),7.636 (5.21), 7.657 (5.27), 7.674 (5.69), 7.678 (6.05), 7.692 (3.06),7.696 (2.52), 8.202 (4.25), 8.206 (4.07), 8.223 (3.90), 8.227 (3.54),8.583 (16.00), 9.155 (4.25), 9.176 (4.13). 205 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.83 (s, 1H), 8.20 (d, J = 9.1 Hz, 1H), L2): Rt= 7.67-7.63 (m, 1H), 7.56 (dd, J = 8.0, 3.94 min; 1.5 Hz, 1H), 7.34 (td,J = 7.8, 2.5 Hz, m/z = 1H), 7.25 (d, J = 7.7 Hz, 1H), 7.23- 568/570 7.12(m, 2H), 6.94-6.80 (m, 3H), 5.39- [M + H]+ 5.31 (m, 1H), 4.38-4 206LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.85 (s, 1H), 8.17 (d, J= 9.1 Hz, 1H), L2): Rt = 7.64 (d, J = 9.1 Hz, 1H), 7.43 (t, J = 1.9 4.15min; Hz, 1H), 7.30-7.17 (m, 4H), 6.92 (td, J = m/z = 7.5, 1.2 Hz, 1H),6.86 (dd, J = 8.3, 1.0 568/570 Hz, 1H), 6.80 (d, J = 7.4 Hz, 1H), 5.40-[M + H]+ 5.33 (m, 1H) 207 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method8.84 (d, J = 1.7 Hz, 1H), 8.14 (dd, J = L2): Rt = 9.1, 1.4 Hz, 1H), 7.62(d, J = 9.2 Hz, 3.41 min; 1H), 7.55 (dd, J = 8.1, 1.5 Hz, 1H), 7.34 m/z= (td, J = 7.8, 2.2 Hz, 1H), 7.26 (d, 1H), 526/528 7.23-7.14 (m, 2H),6.94-6.83 (m, 3H), [M + H]+ 5.38-5.31 (m, 1H 208 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.83 (s, 1H), 8.09 (d, J = 9.1 Hz, 1H), L2): Rt= 7.59 (d, J = 9.1 Hz, 1H), 7.42 (s, 1H), 3.61 min; 7.32-7.15 (m, 4H),6.97-6.82 (m, 3H), m/z = 5.33 (q, J = 5.2 Hz, 1H), 4.38-4.28 (m, 526/5281H), 4.22-4.13 (m, 1H), 3.12 (s, 6H), [M + H]+ 2.42-2.32 (m, 1H 209LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.78 (d, J = 1.7 Hz, 1H),7.57-7.50 (m, L2): Rt = 2H), 7.32-7.17 (m, 5H), 6.94-6.77 3.85 min; (m,3H), 5.40-5.33 (m, 1H), 4.38- m/z = 4.30 (m, 1H), 4.22-4.14 (m, 1H),3.91- 552/554 3.80 (m, 4H), 3.44-3.31 (m, 4H), [M + H]+ 2.44-2.33 (m,1H), 2.25- 210 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.81 (s,1H), 7.61 (dd, J = 8.1, 5.3 Hz, L2): Rt = 1H), 7.47-7.36 (m, 3H),7.32-7.18 4.13 min; (m, 3H), 6.93 (td, J = 7.5, 1.1 Hz, 1H), m/z = 6.86(dd, J = 8.3, 1.0 Hz, 1H), 6.81 (d, J = 552/554 7.5 Hz, 1H), 5.41-5.33(m, 1H), 4.40- [M + H]+ 4.32 (m, 1H), 4. 211 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.24 (Method (d, J = 8.0 Hz, 1H), 8.73 (s, 1H), 8.20, L2): Rt= (d, J = 2.1 Hz, 1H), 7.92 (d, J = 2.1 Hz, 4.39 min; 1H), 7.68 (s, 3H),7.39 (d, J = 7.6 Hz, m/z = 1H), 7.18 (t, J = 7.4 Hz, 1H), 6.93 (t, J =568/570 7.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), [M + H]+ 5.25 (d, J = 7.1212 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.22 (Method (dd, J = 8.0, 5.3 Hz,1H), 8.62 (d, J = 3.1 L2): Rt = Hz, 1H), 8.22 (d, J = 2.4 Hz, 1H), 7.774.12 min; (d, J = 2.3 Hz, 1H), 7.73 (dd, J = 8.0, 1.6 m/z = Hz, 1H),7.46 (td, J = 7.8, 4.5 Hz, 1H), 568/570 7.41-7.33 (m, 2H), 7.16 (t, J =7.0 Hz, [M + H]+ 1H), 6.91 ( 213 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.13(Method (dd, J = 8.1, 5.1 Hz, 1H), 8.54 (d, J = 1.5 L2): Rt = Hz, 1H),8.22 (d, J = 2.4 Hz, 1H), 7.74- 3.75 min; 7.69 (m, 2H), 7.45 (td, J =7.8, 4.4 Hz, m/z = 1H), 7.41-7.31 (m, 2H), 7.20-7.12 526/528 (m, 1H),6.90 (t, J = 7.5 Hz, 1H), 6.78 [M + H]+ (dd, J = 8.2, 1.0 214 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.21 (Method (dd, J = 8.1, 5.5 Hz, 1H), 8.54(d, J = 3.0 L2): Rt = Hz, 1H), 7.67 (dd, J = 8.0, 1.6 Hz, 1H), 3.27 min;7.52 (d, J = 7.3 Hz, 1H), 7.49-7.34 (m, m/z = 3H), 7.33-7.26 (m, 1H),7.16 (t, J = 7.7 548 Hz, 1H), 6.91 (t, δ = 7.4 Hz, 1H), 6.79 [M + H]+(d, J = 8.1 215 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.21 (Method (d, J =8.2 Hz, 1H), 8.62 (s, 1H), 7.68, L2): Rt = (d, J = 7.4 Hz, 1H),7.63-7.55 (m, 3H), 3.56 min; 7.49-7.37 (m, 2H), 7.21-7.14 (m, 1H), m/z =548 6.97-6.90 (m, 1H), 6.83-6.77 (m, 1H), [M + H]+ 5.31-5.23 (m, 1H),4.33- 4.20 (m, 2H), 3.87-3.78 (m 216 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method 2.326 (0.43), 3.568 (16.00), 3.897 (2.36), L1): Rt =3.910 (6.78), 3.954 (0.55), 4.259 (0.56), 0.94 min; 5.263 (0.41), 6.778(0.76), 6.798 (0.79), MS 6.909 (0.76), 6.928 (0.43), 7.141 (0.43),(ESIpos): 7.162 (0.66), 7.359 (0.68), 7.379 (0.61), m/z = 565 7.754(0.48), 7.771 (0.70), 7.792 (0.53), [M + H]+ 7.952 (0.81), 7.970 (0.69),8.151 (1.35), 8.356 (0.70), 8.378 (0.67), 8.396 (1.42), 8.590 (2.23),8.803 (2.18), 9.184 (0.66), 9.205 (0.63). 217 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.12 (Method (d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 7.67 L2): Rt= (d, J = 7.4 Hz, 1H), 7.62-7.56 (m, 3H), 3.04 min; 7.45-7.35 (m, 2H),7.21-7.14 (m, 1H), m/z = 6.97-6.89 (m, 1H), 6.80 (dd, J = 8.2, 506 1.0Hz, 1H), 5.30-5.21 (m, 1H), 4.33- [M + H]+ 4.20 (m, 2H), 2. 218 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.11 (Method (dd, J = 7.9, 5.8 Hz, 1H), 8.49(d, J = 1.8 L2): Rt = Hz, 1H), 7.66 (dd, J = 8.0, 1.6 Hz, 1H), 3.03 min;7.50 (d, J = 7.3 Hz, 1H), 7.45-7.38 (m, m/z = 2H), 7.35 (d, J = 6.8 Hz,1H), 7.33- 506 7.26 (m, 1H), 7.16 (t, J = 7.7 Hz, 1H), [M + H]+ 6.91 (t,J = 7. 219 LC-MS ¹H-NMR (600 MHz, (Method DICHLOROMETHANE-d2) δ [ppm]:L6): Rt = 2.505 (11.27), 3.076 (9.00), 3.332 1.28 min; (16.00), 4.248(0.52), 4.262 (0.80), 5.254 MS (0.50), 6.784 (0.99), 6.797 (1.22), 6.915(ESIpos): (0.81), 6.927 (0.45), 7.055 (0.40), 7.071 m/z = 476 (0.64),7.148 (0.45), 7.161 (0.75), 7.343 [M + H]+ (0.79), 7.356 (0.75), 7.625(0.76), 7.643 (1.22), 8.223 (0.76), 8237 (0.72), 8.548 (1.64), 9.091(0.69), 9.104 (0.67), 10.063 (0.80). 220 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method −0.008 (3.32), 0.008 (3.21), 1.236 (0.84), L6): Rt =1.817 (10.47), 1.834 (9.96), 2.029 (1.50), 1.86 min; 2.037 (1.62), 2.048(1.70), 2.064 (2.32), MS 2.071 (2.04), 2.198 (1.99), 2.210 (1.96),(ESIpos): 2.219 (1.89), 2.231 (1.34), 2.327 (0.87), m/z = 498 2.366(0.64), 2.669 (0.92), 2.710 (0.59), [M + H]+ 3.607 (1.18), 3.634 (0.65),3.880 (16.00), 4.208 (0.97), 4.230 (2.88), 4.257 (4.12), 4.266 (3.48),4.273 (2.88), 4.282 (2.93), 4.294 (1.13), 4.300 (1.21), 5.224 (1.35),5.239 (3.07), 5.258 (3.05), 5.273 (1.35), 6.779 (5.76), 6.799 (6.47),6.894 (2.26), 6.913 (4.68), 6.932 (2.70), 6.998 (2.00), 7.017 (4.09),7.036 (2.35), 7.146 (3.37), 7.165 (5.23), 7.182 (3.02), 7.199 (4.41),7.222 (3.20), 7.274 (2.47), 7.352 (5.14), 7.371 (4.90), 7.465 (0.67),7.486 (0.43), 7.610 (3.69), 7.627 (5.66), 7.676 (4.79), 7.696 (5.53),7.714 (3.21), 8.095 (0.41), 8.114 (0.45), 8.262 (5.39), 8.283 (5.12),8.578 (14.71), 9.146 (2.67). 221 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method 2.072 (1.74), 2.203 (1.62), 2.327 (1.90), L6): Rt = 2.366(1.16), 2.669 (2.05), 2.710 (1.47), 2.11 min; 3.286 (11.07), 3.877(14.20), 4.237 MS (2.72), 4.262 (3.40), 5.249 (2.54), 5.268 (ESIpos):(2.69), 6.781 (4.77), 6.802 (5.41), 6.903 m/z = 518 (2.42), 6.921(5.14), 6.940 (2.97), 7.149 [M + H]+ (2.63), 7.168 (3.98), 7.185 (2.05),7.320 (3.24), 7.343 (6.52), 7.365 (7.89), 7.381 (3.79), 7.480 (3.06),7.487 (4.62), 7.496 (3.43), 7.502 (4.47), 7.510 (2.88), 7.520 (3.15),7.532 (2.66), 7.543 (2.57), 7.686 (2.75), 7.704 (4.93), 7.725 (4.83),7.767 (5.66), 7.782 (3.55), 8.292 (4.37), 8.310 (4.10), 8.624 (16.00),9.156 (4.28), 9.176 (4.41). 222 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 0.008 (1.64), 2.023 (0.54), 2.038 (1.00), L6): Rt = 2.046(1.02), 2.058 (1.08), 2.073 (1.49), 2.07 min; 2.081 (1.28), 2.088(0.94), 2.184 (0.70), MS 2.193 (1.09), 2.205 (1.44), 2.217 (1.35),(ESIpos): 2.227 (1.31), 2.240 (0.90), 2.248 (0.69), m/z = 520 2.327(0.51), 2.366 (0.43), 2.669 (0.49), [M + H]+ 3.259 (1.78), 3.278 (5.13),3.289 (11.26), 3.301 (15.43), 3.312 (16.00), 3.867 (7.04), 3.878(11.75), 3.889 (6.69), 4.209 (0.69), 4.216 (0.81), 4.237 (2.18), 4.245(1.75), 4.264 (2.74), 4.271 (2.61), 4.287 (2.00), 4.306 (0.79), 5.236(0.95), 5.250 (2.07), 5.269 (2.07), 5.283 (0.94), 6.783 (3.72), 6.803(4.15), 6.814 (0.48), 6.906 (1.85), 6.924 (3.92), 6.942 (2.32), 7.148(1.95), 7.152 (2.07), 7.169 (3.35), 7.190 (2.50), 7.200 (1.81), 7.208(1.77), 7.222 (1.73), 7.369 (3.48), 7.387 (3.23), 7.562 (0.70), 7.570(0.83), 7.578 (0.92), 7.585 (1.40), 7.598 (1.38), 7.606 (1.34), 7.611(1.38), 7.619 (0.86), 7.626 (0.75), 7.634 (0.68), 7.707 (2.41), 7.725(3.96), 7.746 (3.74), 7.799 (4.59), 7.814 (2.97), 8.285 (0.81), 8.314(3.61), 8.317 (3.68), 8.335 (3.42), 8.338 (3.29), 8.650 (12.72), 8.724(0.73), 9.169 (3.62), 9.189 (3.54). 223 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method 1.175 (0.49), 1.863 (1.82), 1.911 (2.02), L1): Rt =2.036 (3.68), 2.085 (1.72), 2.163 (2.23), 0.70 min; 2.198 (1.58), 2.327(1.01), 2.669 (1.08), MS 2.709 (0.62), 3.163 (3.07), 3.174 (3.15),(ESIpos): 3.529 (1.52), 3.655 (0.88), 3.763 (1.37), m/z = 518 3.882(2.44), 4.089 (0.62), 4.170 (3.56), [M + H]+ 4.256 (6.88), 4.379 (3.32),5.049 (3.25), 5.211 (2.58), 5.753 (9.32), 6.777 (6.14), 6.796 (6.47),6.881 (3.02), 6.900 (6.29), 6.918 (4.00), 7.140 (3.30), 7.158 (5.04),7.175 (2.77), 7.293 (5.66), 7.311 (5.73), 7.328 (2.80), 7.349 (2.01),7.502 (5.11), 7.651 (2.66), 8.133 (16.00), 8.321 (3.22), 8.355 (6.29),8.737 (1.30), 9.047 (1.75), 12.596 (0.49). 224 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.93), 0.146 (0.80), 2.056 (2.10),L1): Rt = 2.203 (2.12), 2.327 (1.92), 2.366 (1.27), 0.79 min; 2.670(2.02), 2.709 (1.14), 3.893 (16.00), MS 4.229 (3.13), 4.249 (4.61),4.256 (4.76), (ESIpos): 4.495 (1.40), 5.241 (2.87), 5.258 (2.80), m/z =523 6.770 (4.84), 6.790 (5.39), 6.878 (2.36), [M + H]+ 6.896 (5.10),6.914 (3.06), 7.134 (2.59), 7.152 (4.45), 7.171 (2.20), 7.333 (4.66),7.352 (4.38), 7.507 (4.66), 7.525 (7.95), 7.550 (6.37), 7.569 (7.48),7.588 (3.21), 7.691 (2.72), 7.709 (5.02), 7.730 (4.14), 7.788 (5.95),7.804 (4.06), 8.195 (5.05), 8.214 (4.89), 8.287 (4.58), 8.308 (4.38),8.483 (13.31), 9.143 (4.43), 9.164 (4.50), 9.188 (10.17). 225 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.049 (0.55), 2.058 (0.60),2.069 (0.65), L6): Rt = 2.084 (0.92), 2.092 (0.81), 2.200 (0.60), 2.04min; 2.210 (0.84), 2.222 (0.83), 2.231 (0.80), MS 2.244 (0.52), 2.387(16.00), 2.670 (0.42), (ESIpos): 3.246 (0.74), 3.266 (2.20), 3.278(5.05), m/z = 498 3.290 (5.63), 3.652 (0.65), 3.863 (4.10), [M + H]+3.874 (7.04), 3.885 (4.04), 4.225 (0.44), 4.246 (1.32), 4.253 (1.09),4.267 (1.92), 4.276 (1.85), 4.293 (1.21), 4.312 (0.44), 5.246 (0.55),5.260 (1.28), 5.279 (1.30), 5.293 (0.57), 5.754 (0.74), 6.788 (2.36),6.809 (2.64), 6.915 (1.17), 6.933 (2.52), 6.952 (1.46), 7.048 (1.44),7.072 (1.45), 7.156 (1.29), 7.175 (2.10), 7.191 (2.25), 7.222 (4.45),7.376 (2.26), 7.395 (2.06), 7.659 (1.34), 7.678 (2.39), 7.698 (2.06),7.758 (2.87), 7.776 (1.90), 8.243 (2.30), 8.264 (2.08), 8.668 (7.28),9.157 (2.21), 9.178 (2.16). 226 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 3.279 (0.79), 3.291 (1.79), 3.312 (16.00), L6): Rt = 3.868(1.47), 3.879 (2.45), 3.889 (1.39), 2.10 min; 4.237 (0.46), 4.258(0.61), 4.286 (0.43), MS 5.249 (0.45), 5.268 (0.45), 5.754 (0.77),(ESIpos): 6.781 (0.85), 6.801 (0.94), 6.904 (0.42), m/z = 518 6.922(0.86), 6.941 (0.50), 7.149 (0.43), [M + H]+ 7.167 (0.75), 7.304 (0.41),7.324 (1.03), 7.344 (0.75), 7.366 (0.78), 7.385 (1.17), 7.400 (0.72),7.644 (0.68), 7.695 (0.42), 7.713 (0.86), 7.734 (0.84), 7.754 (1.05),7.769 (0.52), 8.300 (0.71), 8.318 (0.70), 8.629 (2.54), 9.157 (0.74),9.177 (0.72). 227 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.030(1.38), 2.038 (1.48), 2.053 (1.64), L6): Rt = 2.064 (2.14), 2.072(1.92), 2.187 (1.53), 2.02 min; 2.199 (1.97), 2.210 (1.94), 2.220(1.83), MS 2.233 (1.30), 2.669 (0.41), 3.254 (2.20), (ESIpos): 3.287(11.31), 3.876 (16.00), 4.213 m/z = 518 (1.15), 4.234 (3.07), 4.241(2.68), 4.255 [M + H]+ (4.56), 4.264 (4.46), 4281 (2.83), 4.300 (1.09),5.229 (1.31), 5.244 (2.94), 5.262 (2.90), 5.277 (1.27), 5.753 (3.72),6.777 (4.98), 6.798 (5.63), 6.896 (2.63), 6.914 (5.47), 6.933 (3.20),7.144 (2.90), 7.163 (4.73), 7.182 (2.38), 7.244 (2.61), 7.265 (2.55),7.289 (2.22), 7.297 (1.96), 7.311 (3.96), 7.318 (3.43), 7.332 (2.42),7.340 (2.20), 7.355 (5.09), 7.374 (4.69), 7.573 (3.19), 7.586 (3.35),7.595 (3.06), 7.608 (2.68), 7.666 (2.45), 7.683 (11.68), 7.703 (5.74),7.721 (2.06), 8.279 (4.22), 8.283 (4.22), 8.299 (3.93), 8.303 (3.83),8.598 (13.90), 9.158 (4.80), 9.178 (4.64). 228 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 2.050 (0.48), 2.057 (0.51), 2.071 (0.57), L6):Rt = 2.085 (0.76), 2.092 (0.66), 2.199 (0.53), 2.11 min; 2.210 (0.69),2.221 (0.68), 2.231 (0.64), MS 2.244 (0.44), 3.245 (0.65), 3.265 (1.89),(ESIpos): 3.276 (4.16), 3.288 (4.44), 3.822 (16.00), m/z = 530 3.844(0.52), 3.864 (3.56), 3.874 (5.85), [M + H]+ 3.884 (3.40), 4.246 (1.08),4.253 (0.91), 4.267 (1.58), 4.276 (1.53), 4.293 (0.98), 5.244 (0.47),5.258 (1.07), 5.277 (1.07), 5.291 (0.47), 5.754 (1.95), 6.788 (1.90),6.809 (2.13), 6.916 (0.97), 6.935 (2.06), 6.954 (1.21), 7.062 (2.64),7.094 (2.80), 7.156 (1.06), 7.175 (1.70), 7.197 (3.47), 7.378 (1.82),7.397 (1.68), 7.662 (1.05), 7.682 (1.95), 7.701 (1.50), 7.782 (2.37),7.799 (1.71), 8.251 (1.97), 8.272 (1.79), 8.677 (5.49), 9.160 (1.84),9.180 (1.81). 229 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (0.69), −0.008 (5.65), 0.008 L1): Rt = (5.56), 0.146 (0.66),1.997 (0.61), 2.012 0.76 min; (1.19), 2.023 (1.58), 2.031 (1.41), 2.044MS (2.52), 2.059 (2.38), 2.072 (0.97), 2.127 (ESIpos): (0.89), 2.141(2.46), 2.155 (2.88), 2.169 m/z = 443 (1.49), 2.191 (1.36), 2.203(0.61), 2.327 [M + H]+ (1.22), 2.366 (1.05), 2.523 (3.99), 2.669 (1.30),2.709 (1.13), 3.057 (15.92), 3.069 (16.00), 4.247 (5.37), 4.259 (8.78),4.273 (5.09), 5.218 (1.36), 5.233 (3.02), 5.253 (3.02), 5.267 (1.38),6.780 (5.48), 6.800 (6.06), 6.889 (2.85), 6.891 (2.82), 6.908 (6.03),6.926 (3.63), 7.139 (2.88), 7.143 (3.02), 7.160 (4.73), 7.178 (2.35),7.182 (2.30), 7.304 (5.04), 7.322 (4.71), 7.414 (1.99), 7.434 (5.79),7.446 (4.98), 7.464 (7.53), 7.484 (3.74), 7.508 (4.98), 7.511 (9.38),7.515 (6.42), 7.530 (7.11), 7.553 (3.24), 7.632 (8.14), 7.636 (4.76),7.667 (5.87), 7.684 (4.76), 7.756 (1.49), 8.133 (6.12), 8.233 (1.00),8.312 (4.40), 8.333 (4.21), 8.424 (15.67), 8.963 (3.43), 8.983 (3.35),12.706 (0.72). 230 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method2.039 (0.49), 2.074 (0.74), 2.206 (0.68), L6): Rt = 2.217 (0.65), 2.228(0.62), 3.247 (0.58), 1.93 min; 3.279 (4.26), 3.291 (4.54), 3.861(3.48), MS 3.872 (5.83), 3.883 (3.38), 3.919 (16.00), (ESIpos): 4.240(1.05), 4.247 (0.85), 4.261 (1.44), m/z = 532 4.288 (0.95), 5.239(0.43), 5.254 (1.04), [M + H]+ 5.273 (1.05), 5.287 (0.48), 5.754 (5.28),6.783 (2.11), 6.803 (2.33), 6.907 (0.98), 6.926 (2.11), 6.945 (1.22),7.152 (1.05), 7.172 (2.27), 7.192 (1.76), 7.202 (1.25), 7.220 (1.17),7.288 (1.26), 7.305 (1.27), 7.318 (1.25), 7.334 (1.22), 7.367 (1.77),7.386 (1.63), 7.661 (0.93), 7.680 (2.04), 7.700 (1.95), 7.722 (2.44),7.738 (1.14), 8.258 (1.70), 8.276 (1.55), 8.620 (6.28), 9.153 (1.82),9.173 (1.77). 231 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.072(0.90), 2.204 (0.83), 2.327 (0.69), L6): Rt = 2.366 (0.42), 2.408(16.00) 2.670 (0.67), 2.25 min; 3.282 (5.02), 3.294 (5.70), 3.862(3.95), MS 3.873 (6.80), 3.885 (3.85), 4.237 (1.27), (ESIpos): 4.259(1.58), 4.285 (1.15), 5.249 (1.24), m/z = 532 5.268 (1.26), 6.783(2.54), 6.803 (2.69), [M + H]+ 6.906 (1.22), 6.924 (2.41), 6.941 (1.48),7.147 (1.32), 7.169 (1.98), 7.186 (1.00), 7.326 (2.64), 7.352 (2.75),7.365 (2.13), 7.381 (1.93), 7.448 (3.44), 7.465 (3.40), 7.674 (1.50),7.692 (2.59), 7.713 (2.56), 7.743 (2.91), 7.757 (1.61), 8.273 (2.14),8.277 (2.20), 8.294 (2.00), 8.612 (8.94), 9.154 (2.17), 9.175 (2.13).232 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.033 (0.68), 2.041(0.74), 2.052 (0.79), L6): Rt = 2.068 (1.07), 2.075 (0.94), 2.189(0.70), 1.90 min; 2.201 (0.97), 2.213 (0.96), 2.222 (0.91), MS 2.235(0.63), 2.327 (0.60), 2.366 (0.45), (ESIpos): 2.669 (0.68), 2.709(0.48), 3.254 (0.88), m/z = 532 3.273 (2.55), 3.286 (5.77), 3.588(15.32), [M + H]+ 3.591 (16.00), 3.864 (4.82), 3.875 (8.30), 3.886(4.64), 4.213 (0.57), 4.234 (1.64), 4.241 (1.30), 4.261 (2.03), 4.269(1.72), 4.276 (1.38), 4.285 (1.39), 4.304 (0.57), 5.232 (0.65), 5.246(1.48), 5.265 (1.51), 5.279 (0.66), 6.782 (2.77), 6.802 (3.06), 6.901(1.38), 6.919 (2.88), 6.936 (1.69), 7.032 (0.93), 7.037 (0.97), 7.048(1.14), 7.053 (2.04), 7.059 (1.39), 7.069 (1.33), 7.075 (1.25), 7.145(1.39), 7.149 (1.51), 7.167 (2.40), 7.184 (2.10), 7.204 (1.50), 7.227(1.53), 7.249 (0.88), 7.354 (2.50), 7.372 (2.32), 7.637 (0.62), 7.643(1.31), 7.655 (4.76), 7.659 (6.97), 7.678 (3.56), 7.695 (1.24), 8.249(2.35), 8.255 (2.38), 8.269 (2.16), 8.274 (2.15), 8.597 (9.66), 9.143(2.61), 9.163 (2.55). 233 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.20 (Method(d, J = 8.1 Hz, 1H), 8.71 (s, 1H), 8.46 L2): Rt = (d, J = 8.9 Hz, 1H),7.98 (d, J = 9.1 Hz, 4.22 min; 1H), 7.70 (t, J = 1.9 Hz, 1H), 7.40-7.30m/z = 602 (m, 3H), 7.20-7.13 (m, 1H), 6.95-6.88 (Cl2 (m, 1H), 6.82-6.76(m, 1H), 5.28-5.20 pattern) (m, 1H), 4.32 [M + H]+ 234 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.59), −0.008 (5.31), 0.008 L1):Rt = (4.81), 0.146 (0.56), 2.049 (1.06), 2.057 1.10 min; (1.15), 2.069(1.17), 2.084 (1.68), 2.091 MS (1.48), 2.198 (1.12), 2.211 (1.57), 2.223(ESIpos): (1.45), 2.233 (1.45), 2.246 (0.95), 2.327 m/z = 502 (1.17),2.366 (1.12), 2.523 (3.97), 2.669 [M + H]+ (1.34), 2.710 (1.17), 3.249(1.26), 3.268 (4.20), 3.280 (9.93), 3.291 (10.83), 3.651 (1.90), 3.865(7.83), 3.876 (13.26), 3.887 (7.52), 4.225 (0.87), 4.245 (2.52), 4.253(1.99), 4.267 (3.33), 4.293 (2.21), 4.312 (0.81), 5.245 (1.03), 5.259(2.35), 5.279 (2.38), 5.293 (1.06), 6.789 (4.36), 6.809 (4.90), 6.917(2.18), 6.933 (4.64), 6.951 (2.80), 7.154 (2.49), 7.157 (2.57), 7.175(4.00), 7.193 (1.99), 7.247 (1.76), 7.253 (1.29), 7.265 (1.59), 7.271(3.41), 7.277 (2.49), 7.294 (1.87), 7.300 (1.45), 7.319 (4.84), 7.324(5.48), 7.340 (6.01), 7.356 (1.23), 7.377 (4.17), 7.396 (3.86), 7.681(3.13), 7.700 (4.62), 7.720 (4.20), 7.827 (4.95), 7.831 (5.20), 7.845(4.06), 7.848 (3.92), 8.273 (4.31), 8.276 (4.39), 8.295 (4.11), 8.693(16.00), 9.165 (4.20), 9.185 (4.11). 235 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method 2.091 (2.67), 2.220 (2.73), 2.327 (2.60), L1): Rt =2.367 (5.33), 2.668 (4.62), 2.710 (5.79), 1.29 min; 3.882 (16.00), 4.244(3.32), 4.266 (4.62), MS 5.255 (3.12), 6.789 (4.36), 6.809 (4.81),(ESIpos): 6.915 (2.34), 6.934 (4.75), 6.952 (2.73), m/z = 568 7.155(2.80), 7.174 (4.29), 7.195 (2.15), [M + H]+ 7.381 (4.62), 7.399 (4.16),7.706 (2.47), 7.724 (4.62), 7.743 (2.99), 7.886 (7.28), 7.903 (12.75),7.985 (7.15), 8.302 (4.75), 8.323 (4.36), 8.693 (9.95), 9.174 (4.29),9.194 (4.10). 236 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (2.92), 0.008 (2.76), 1.236 (1.50), L6): Rt = 1.259 (1.23), 1.299(0.85), 1.983 (0.59), 1.38 min; 1.996 (1.10), 2.008 (1.36), 2.016(1.23), MS 2.030 (2.09), 2.044 (1.95), 2.057 (0.80), (ESIpos): 2.118(0.75), 2.132 (2.09), 2.146 (2.34), m/z = 462 2.161 (1.32), 2.181(1.28), 2.195 (0.53), [M + H]+ 2.300 (1.82), 2.327 (0.64), 2.366 (0.61),2.523 (2.31), 2.669 (0.73), 2.709 (0.69), 3.057 (12.33), 3.070 (12.39),(12.39), 3.341 (0.78), 3.370 (0.41), 3.382 (0.48), 3.874 (0.57), 4.237(4.47), 4.249 (7.39), 4.264 (4.32), 4.482 (1.02), 4.497 (1.07), 4.858(10.93), 5.146 (0.64), 5.206 (1.12), 5.221 (2.49), 5.240 (2.47), 5.255(1.12), 5.359 (0.43), 6.772 (4.55), 6.793 (4.96), 6.878 (2.39), 6.880(2.39), 6.896 (4.95), 6.899 (4.90), 6.915 (2.97), 6.917 (2.87), 7.132(2.42), 7.135 (2.57), 7.153 (4.02), 7.170 (2.01), 7.174 (1.96), 7.232(0.48), 7.250 (0.41), 7.274 (1.85), 7.293 (8.65), 7.312 (7.85), 7.327(1.21), 7.333 (1.21), 7.345 (3.29), 7.355 (13.29), 7.365 (4.96), 7.376(1.77), 7.527 (1.53), 7.545 (2.97), 7.566 (2.27), 7.591 (1.64), 7.608(2.84), 7.629 (4.71), 7.647 (2.65), 7.765 (1.79), 8.133 (0.54), 8.367(16.00), 8.391 (3.06), 8.958 (2.52), 8.979 (2.52), 10.023 (0.51), 11.746(5.38). 237 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.150(0.77), 0.146 (0.83), 0.853 (0.66), L6): Rt = 1.235 (5.81), 1.259(3.13), 1.298 (2.19), 1.57 min; 1.985 (1.63), 1.998 (1.98), 2.019(2.99), MS 2.035 (2.68), 2.126 (2.85), 2.140 (3.27), (ESIpos): 2.159(2.19), 2.175 (1.95), 2.327 (1.98), m/z = 512 2.366 (1.29), 2.669(2.37), 2.710 (1.57), [M + H]+ 3.051 (15.79), 3.061 (16.00), 3.370(1.57), 3.382 (1.70), 3.395 (1.15), 3.413 (0.73), 3.508 (0.97), 3.520(1.18), 3.534 (0.94), 3.561 (1.11), 3.574 (1.22), 4.233 (6.02), 4.245(10.37), 4.259 (6.33), 4.482 (2.37), 4.496 (2.33), 4.858 (9.39), 5.131(0.66), 5.146 (1.29), 5.160 (0.63), 5.198 (1.74), 5.213 (3.69), 5.233(3.76), 5.247 (1.77), 5.359 (1.22), 6.768 (7.10), 6.788 (7.93), 6.874(3.27), 6.893 (7.03), 6.911 (4.24), 7.132 (3.58), 7.150 (5.95), 7.171(2.85), 7.219 (0.56), 7.286 (6.26), 7.307 (11.55), 7.320 (3.51), 7.355(11.93), 7.365 (3.90), 7.393 (4.45), 7.398 (4.56), 7.418 (4.73), 7.424(4.42), 7.460 (0.94), 7.518 (4.42), 7.536 (7.55), 7.556 (7.23), 7.585(8.59), 7.601 (5.11), 7.614 (3.20), 7.634 (2.19), 7.706 (1.01), 7.724(1.50), 7.774 (2.57), 7.871 (11.10), 7.877 (10.96), 7.910 (2.57), 7.927(2.23), 7.954 (0.59), 8.022 (0.70), 8.139 (1.18), 8.340 (15.06), 8.374(5.91), 8.394 (5.57), 8.427 (0.73), 8.946 (4.28), 8.967 (4.28), 10.022(3.72), 11.746 (4.21). 238 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (0.56), 0.008 (0.52), 2.523 (0.53), L1): Rt = 3.277(0.80), 3.290 (1.68), 3.310 (16.00), 1.05 min; 3.333 (0.41), 3.867(1.46), 3.877 (2.48), MS 3.889 (1.37), 4.232 (0.50), 4.253 (0.68),(ESIpos): 4.264 (0.64), 4.271 (0.44), 4.280 (0.43), m/z = 518 5.241(0.43), 5.260 (0.43), 6.777 (0.84), [M + H]+ 6.798 (0.93), 6.912 (0.84),6.930 (0.49), 7.141 (0.44), 7.145 (0.46), 7.162 (0.73), 7.354 (0.77),7.371 (0.72), 7.447 (0.89), 7.456 (1.29), 7.468 (0.84), 7.475 (0.99),7.668 (0.48), 7.680 (1.31), 7.685 (1.24), 7.690 (1.31), 7.709 (1.11),7.727 (0.46), 8.286 (0.80), 8.291 (0.82), 8.306 (0.74), 8.311 (0.72),8.589 (2.41), 9.154 (0.41). 239 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 2.278 (3.88), 3.284 (1.78), 3.297 (2.06), L1): Rt = 3.310(16.00), 3.875 (2.72), 4.236 (0.51), 1.18 min; 4.258 (0.65), 4.285(0.46), 5.248 (0.49), MS 5.267 (0.50), 6.782 (0.98), 6.801 (1.08),(ESIpos): 6.902 (0.49), 6.921 (0.99), 6.939 (0.59), m/z = 532 7.150(0.51), 7.168 (0.80), 7.186 (0.41), [M + H]+ 7.264 (0.62), 7.271 (0.72),7.279 (0.66), 7.286 (0.65), 7.367 (0.86), 7.385 (0.82), 7.442 (0.63),7.452 (0.65), 7.673 (0.52), 7.691 (1.06), 7.711 (1.07), 7.732 (1.23),7.746 (0.57), 8.279 (0.87), 8.299 (0.80), 8.624 (3.45), 9.154 (0.86),9.175 (0.85). 240 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (0.50), 0.008 (0.44), 2.345 (4.63), L1): Rt = 3.275 (0.72), 3.287(1.65), 3.299 (1.87), 1.19 min; 3.310 (16.00), 3.865 (1.37), 3.876(2.36), MS 3.888 (1.31), 4.237 (0.45), 4.259 (0.60), (ESIpos): 4.269(0.56), 5.249 (0.43), 5.268 (0.43), m/z = 532 6.782 (0.83), 6.803(0.90), 6.924 (0.83), [M + H]+ 6.941 (0.49), 7.147 (0.41), 7.150 (0.43),7.167 (0.71), 7.184 (0.80), 7.192 (0.61), 7.198 (0.56), 7.367 (0.70),7.385 (0.66), 7.447 (0.53), 7.451 (0.52), 7.463 (0.55), 7.682 (0.43),7.700 (0.93), 7.720 (1.01), 7.731 (1.02), 7.735 (1.15), 7.748 (0.49),8.284 (0.71), 8.288 (0.72), 8.305 (0.69), 8.309 (0.65), 8.626 (3.04),9.154 (0.75), 9.175 (0.74). 241 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.219 (16.00), 1.414 (0.57), 1.908 (0.65), L1): Rt = 1.924(0.64), 1.941 (0.52), 1.959 (0.45), 1.38 min; 2.501 (12.69), 2.889(0.42), 3.164 (0.96), MS 3.174 (0.90), 5.530 (0.45), 5.549 (0.44),(ESIpos): 7.233 (0.64), 7.241 (0.67), 7.250 (1.06), m/z = 602 7.271(0.78), 7.448 (0.44), 7.456 (0.48), [M + H]+ 7.469 (0.40), 7.639 (5.38),7.652 (0.69), 7.672 (0.56), 7.809 (0.75), 7.826 (0.60), 8.314 (0.64),8.335 (0.58), 8.687 (2.17), 9.077 (0.63), 9.097 (0.60). 242 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 1.198 (16.00), 1.918 (0.63), 1.932(0.85), L6): Rt = 1.945 (0.51), 4.260 (0.44), 6.788 (0.61), 1.39 min;6.808 (0.69), 6.939 (0.64), 7.186 (0.52), MS 7.394 (0.55), 7.412 (0.51),7.638 (5.73), (ESIpos): 7.656 (0.62), 7.676 (0.53), 7.815 (0.70), m/z =618 7.832 (0.56), 8.315 (0.60), 8.334 (0.55), [M + H]+ 8.684 (2.06),9.236 (0.58), 9.257 (0.57). 243 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (0.59), 0.008 (0.57), 1.194 (16.00), L6): Rt = 1.209(0.55), 2.041 (0.61), 2.056 2.63 min; (0.60), 2.067 (0.49), 2.086(0.43), 4.279 MS (0.48), 4.293 (0.85), 4.305 (0.52), 6.785 (ESIpos):(0.57), 6.804 (0.64), 6.881 (0.61), 7.163 m/z = 618 (0.49), 7.292(0.52), 7.310 (0.49), 7.643 [M + H]+ (3.60), 7.659 (0.61), 7.680 (0.50),7.819 (0.64), 7.834 (0.53), 8.352 (0.56), 8.371 (0.52), 8.689 (2.03),9.172 (0.56), 9.192 (0.54). 244 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (2.63), 0.008 (2.13), 1.862 (1.03), L6): Rt = 1.885(0.89), 1.898 (0.91), 2.002 (0.76), 1.27 min; 2.023 (1.37), 2.034(1.59), 2.054 (1.51), MS 2.156 (0.85), 2.170 (1.04), 2.185 (0.86),(ESIpos): 2.201 (0.61), 2.311 (0.43), 2.327 (0.46), m/z = 498 2.376(16.00), 2.392 (2.37), 2.669 (0.43), [M + H]+ 3.033 (0.41), 3.192(0.48), 3.205 (0.71), 3.213 (0.64), 3.228 (0.83), 3.305 (2.36), 3.461(0.98), 3.489 (1.75), 3.516 (0.92), 3.691 (0.53), 3.707 (1.16), 3.728(0.79), 3.788 (0.70), 3.805 (0.71), 3.821 (0.86), 3.831 (1.06), 3.844(1.78), 3.857 (1.54), 3.871 (1.20), 3.883 (0.74), 4.163 (3.03), 4.258(2.73), 4.266 (3.03), 4.279 (1.47), 4.374 (1.56), 5.215 (0.85), 5.227(1.09), 5.247 (0.91), 5.260 (0.41), 6.780 (2.43), 6.799 (2.76), 6.891(1.22), 6.910 (2.68), 6.928 (1.78), 7.014 (1.49), 7.038 (1.51), 7.144(1.33), 7.162 (2.39), 7.179 (2.31), 7.205 (5.13), 7.253 (0.67), 7.305(2.22), 7.324 (2.00), 7.450 (1.52), 7.469 (2.29), 7.489 (1.84), 7.638(2.80), 7.653 (2.35), 8.144 (10.55), 8.227 (2.36), 8.248 (2.20), 8.418(4.54), 8.423 (4.98), 8.786 (1.00), 9.041 (1.92), 9.061 (1.88). 245LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.77), −0.008(6.72), 0.008 L6): Rt = (6.90), 0.146 (0.79), 1.055 (0.79), 1.862 1.24min; (1.68), 1.885 (1.70), 1.895 (1.97), 2.006 MS (1.70), 2.027 (2.95),2.040 (3.20), 2.060 (ESIpos): (1.95), 2.072 (1.32), 2.085 (1.63), 2.145m/z = 532 (1.45), 2.159 (1.57), 2.175 (1.52), 2.327 [M + H]+ (1.52),2.365 (1.04), 2.669 (1.41), 2.709 (0.77), 2.976 (0.89), 3.005 (1.41),3.073 (1.32), 3.083 (1.34), 3.113 (0.93), 3.164 (2.00), 3.177 (2.34),3.187 (2.36), 3.200 (2.22), 3.304 (2.68), 3.466 (1.97), 3.496 (2.86),3.524 (1.75), 3.695 (1.16), 3.719 (1.95), 3.737 (1.34), 3.788 (0.68),3.810 (1.16), 3.828 (1.48), 3.848 (2.50), 3.864 (2.18), 3.874 (3.20),3.889 (1.95), 3.900 (1.23), 3.937 (0.43), 4.163 (11.73), 4.255 (5.47),4.374 (2.88), 5.226 (1.84), 5.266 (0.59), 6.772 (4.31), 6.791 (5.17),6.809 (1.38), 6.879 (2.04), 6.899 (4.70), 6.916 (3.56), 6.935 (0.70),7.016 (1.41), 7.032 (2.79), 7.048 (1.86), 7.084 (0.86), 7.105 (0.68),7.137 (2.31), 7.156 (4.45), 7.177 (3.63), 7.204 (2.20), 7.225 (1.41),7.242 (0.68), 7.287 (3.50), 7.306 (3.22), 7.342 (0.93), 7.359 (0.98),7.448 (2.31), 7.466 (3.93), 7.487 (3.79), 7.526 (5.13), 7.541 (3.06),7.688 (1.57), 7.696 (1.68), 7.705 (3.70), 8.204 (16.00), 8.276 (4.47),8.297 (3.47), 8.360 (10.80), 8.716 (4.06), 9.014 (1.95), 9.027 (2.34),9.035 (2.07), 9.047 (1.97), 9.155 (0.86), 9.176 (0.79). 246 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (1.15), 0.008 (1.23), 1.862(0.77), L6): Rt = 1.876 (0.55), 1.888 (0.61), 1.900 (0.68), 1.21 min;1.908 (0.60), 1.997 (0.55), 2.020 (0.91), MS 2.030 (1.23), 2.039 (0.98),2.049 (0.99), (ESIpos): 2.061 (0.58), 2.150 (0.56), 2.165 (0.68), m/z =532 2.180 (0.59), 2.195 (0.42), 2.523 (0.68), [M + H]+ 3.169 (1.12),3207 (0.44), 3.230 (0.51), 3.305 (0.99), 3.471 (0.58), 3.498 (1.19),3.525 (0.73), 3.655 (0.44), 3.699 (0.41), 3.723 (0.82), 3.736 (0.56),3.743 (0.59), 3.803 (0.57), 3.820 (0.55), 3.828 (0.57), 3.835 (0.56),3.846 (1.52), 3.858 (1.38), 3.873 (0.89), 3.885 (1.01), 3.896 (0.64),3.911 (16.00), 3.924 (2.42), 4.160 (2.23), 4.247 (1.69), 4.253 (2.01),4.259 (1.98), 4.374 (1.08), 5.210 (0.63), 5.219 (0.73), 5.231 (0.77),5.240 (0.56), 6.776 (1.78), 6.794 (1.90), 6.796 (1.93), 6.886 (0.87),6.904 (1.89), 6.923 (1.25), 7.140 (1.08), 7.148 (1.24), 7.158 (1.75),7.166 (1.29), 7.175 (1.95), 7.194 (1.17), 7.263 (1.08), 7.280 (1.12),7.294 (2.16), 7.311 (1.67), 7.451 (1.14), 7.469 (1.65), 7.490 (1.47),7.599 (1.95), 7.615 (1.51), 8.140 (6.92), 8.264 (1.70), 8.276 (0.41),8.286 (1.58), 8.370 (4.09), 8.372 (3.69), 8.738 (0.72), 9.025 (1.07),9.032 (0.96), 9.046 (1.07), 9.053 247 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (1.77), 0.008 (1.62), 1.754 (1.10), L6): Rt =3.086 (16.00), 4.249 (0.89), 4.257 (0.88), 1.82 min; 5.230 (0.54), 6.777(1.07), 6.797 (1.20), MS 6.890 (0.49), 6.908 (1.04), 6.926 (0.63),(ESIpos): 7.143 (0.51), 7.160 (0.85), 7.178 (0.42), m/z = 478 7.339(0.86), 7.357 (0.83), 7.586 (0.46), [M + H]+ 7.600 (0.44), 7.669 (0.76),7.686 (1.09), 7.708 (1.03), 7.788 (1.10), 7.803 (0.82), 8.233 (0.62),8.303 (1.02), 8.321 (1.02), 8.550 (2.65), 9.066 (0.59), 9.088 (0.56).248 3.41 ¹H-NMR (399, 9532 MHz, DMSO): δ = 8.8586 (3.81); 8.8384 (3.7);8.7959 (0.89); 8.6133 (16); 8.3145 (0.54); 8.2003 (5.17); 8.1796 (6.09);8.1605 (0.57); 8.1408 (0.42); 8.1194 (0.37); 7.7297 (2.81); 7.7117(6.49); 7.6916 (5.56); 7.674 (8.15); 7.6572 (3.78); 7.5658 (3.63);7.5485 (5.05); 7.5233 (0.53); 7.4659 (2.08); 7.4474 (5.9); 7.4352(6.58); 7.4201 (10.6); 7.401 (7.64); 7.3696 (4.28); 7.1855 (0.44);7.1677 (2.86); 7.1479 (5.7); 7.1292 (3.51); 6.9273 (3.58); 6.9086(6.16); 6.8902 (3.03); 6.7978 (0.51); 6.7802 (7.27); 6.76 (6.4); 5.3045(0.38); 5.2303 (1.66); 5.215 (3.56); 5.1967 (3.61); 5.1821 (1.57);4.2872 (1.16); 4.2678 (3.46); 4.2545 (6.45); 4.2294 (3.77); 4.209(1.09); 4.0558 (0.79); 4.0381 (2.17); 4.0204 (2.21); 4.0027 (0.72);3.7036 (0.64); 3.4987 (41.77); 3.4769 (2.9); 3.3203 (34.08); 3.2937(39.4); 32522 (2.31); 2.6698 (1.63); 2.5008 (284.9); 2.3275 (1.72);2.162 (2.06); 2.1511 (2.35); 2.1408 (2.37); 2.0491 (2.34); 2.0417(2.67); 2.0242 (2.02); 2.0072 (1.6); 1.9885 (9.27); 1.2351 (0.38);1.1928 (2.3); 1.175 (4.51); 1.1572 (2.22); −0.0001 (28.96); −0.0051(8.21) 249 3.99 ¹H-NMR (399, 9532 MHz, DMSO): δ = 8.8722 (2.6); 8.8534(4.17); 8.8356 (2.45); 8.6283 (16); 8.3151 (0.4); 8.2158 (4.05); 8.1962(4.44); 7.7428 (2.44); 7.7248 (7.39); 7.7193 (7); 7.7157 (6.57); 7.7049(13.43); 7.6994 (14.58); 7.6871 (2.66); 7.4723 (2.01); 7.4623 (2.04);7.453 (4.25); 7.4429 (3.96); 7.4331 (2.87); 7.4227 (5.23); 7.3996(4.11); 7.3619 (3.39); 7.3461 (5.37); 7.3279 (2.31); 7.1671 (2.41);7.1484 (5.12); 7.1288 (3.22); 6.9268 (2.74); 6.9082 (4.77); 6.8896(2.27); 6.7797 (6.81); 6.7595 (6.15); 5.2265 (1.31); 5.2117 (3.11);5.1938 (3.02); 5.1779 (1.3); 4.2866 (1.01); 4.2674 (3.19); 4.2527(5.74); 4.245 (5.26); 4.2269 (3.27); 4.2067 (0.94); 4.0557 (0.4); 4.0377(1.21); 4.0198 (1.19); 4.0022 (0.41); 3.4991 (33.03); 3.3194 (26.59);3.2941 (42.87); 2.6699 (1.31); 2.6325 (1.42); 2.5047 (173.21); 2.5007(220.51); 2.4968 (169.05); 2.3277 (1.28); 2.1552 (1.78); 2.1467 (1.98);2.1354 (1.9); 2.0536 (1.58); 2.0461 (2.06); 2.0382 (2.41); 2.0293(1.73); 2.0221 (1.72); 2.0124 (1.48); 2.0033 (1.41); 1.9882 (5.54);1.3973 (0.39); 1.1925 (1.29); 1.1746 (2.48); 1.1569 (1.25); −0.0002(29.01) 250 4.87 ¹H-NMR (399, 9532 MHz, DMSO): δ = 8.8638 (2.16); 8.8431(2.2); 8.7403 (8.57); 8.3148 (0.35); 8.2096 (2.24); 8.2067 (2.37);8.1883 (2.63); 8.1855 (2.59); 7.8776 (2.13); 7.8749 (2.29); 7.8598(2.88); 7.8571 (2.85); 7.7436 (2.21); 7.7227 (2.59); 7.7045 (1.68);7.6508 (16); 7.4465 (2.08); 7.4284 (2.26); 7.181 (0.97); 7.1773 (1.02);7.16 (2.16); 7.1425 (1.33); 7.1389 (1.31); 6.9459 (1.54); 6.9275 (2.62);6.9086 (1.24); 6.7901 (2.91); 6.7708 (2.62); 5.246 (0.57); 5.2307(1.34); 5.2111 (1.31); 5.1962 (0.59); 4.2989 (0.4); 4.2923 (0.34);4.2803 (1.25); 4.2648 (2.35); 4.2564 (2.18); 4.2462 (1.28); 4.238(1.35); 4.2183 (0.41); 3.4928 (21.15); 3.3195 (28.27); 3.2832 (18.37);2.6707 (0.76); 2.5055 (99.44); 2.5013 (134.25); 2.4971 (103.62); 2.3283(0.8); 2.1902 (0.48); 2.1778 (0.73); 2.169 (0.84); 2.1575 (0.88); 2.1451(0.68); 2.0765 (0.62); 2.0678 (0.83); 2.0606 (0.98); 2.0512 (0.71);2.0439 (0.7); 2.034 (0.6); 2.0254 (0.58); 1.3977 (0.96); −0.0002 (18.38)251 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 0.832 (0.78), 0.872(0.63), 1.225 (1.56), L4): Rt = 1.239 (2.99), 1.254 (2.68), 1.285(0.49), 2.76 min; 2.012 (5.28), 2.125 (0.61), 2.136 (1.21), MS 2.143(1.50), 2.153 (1.46), 2.162 (2.19), (ESIpos): 2.172 (2.02), 2.181(0.79), 2.253 (0.83), m/z = 523 2.265 (1.86), 2.277 (2.20), 2.290(1.59), [M + H]+ 2.306 (1.15), 2.317 (0.53), 3.149 (1.15), 3.179(10.27), 3.371 (1.35), 3.379 (2.47), 3.394 (3.63), 3.403 (5.57), 3.412(3.40), 3.423 (3.54), 3.431 (5.99), 3.440 (3.84), 3.456 (2.58), 3.465(1.35), 3.947 (9.47), 3.955 (15.45), 3.964 (8.40), 4.057 (0.45), 4.071(1.28), 4.086 (1.30), 4.100 (0.49), 4.278 (4.64), 4.288 (6.97), 4.294(4.07), 4.299 (4.02), 5.328 (1.19), 5.339 (2.69), 5.354 (2.69), 5.365(1.19), 5.443 (0.90), 5.448 (1.32), 6.779 (4.78), 6.796 (5.27), 6.863(2.26), 6.878 (4.67), 6.893 (2.69), 7.124 (2.45), 7.139 (3.94), 7.154(2.07), 7.309 (4.10), 7.324 (3.86), 7.506 (4.42), 7.520 (5.68), 7.613(3.66), 7.628 (5.26), 7.644 (3.03), 7.658 (2.51), 7.672 (4.37), 7.689(3.02), 7.811 (6.72), 7.814 (7.13), 7.818 (4.61), 7.821 (6.00), 7.825(7.74), 7.828 (6.36), 7.831 (5.94), 8.107 (5.62), 8.123 (5.32), 8.315(4.53), 8.332 (4.30), 8.604 (16.00), 9.065 (6.90), 9.103 (2.34), 9.118(2.15). 252 2.23 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.0791 (1.76); 9.0587(1.8); 8.5559 (7.36); 8.1993 (1.5); 8.1925 (1.41); 8.1814 (1.62); 8.1744(1.67); 7.6235 (0.75); 7.6058 (2.84); 7.5938 (3.05); 7.5875 (6.22);7.5767 (0.85); 7.5518 (1.11); 7.5301 (1.53); 7.4508 (0.54); 7.4455(0.73); 7.4326 (1.69); 7.4272 (2.02); 7.4216 (1.16); 7.4156 (2.28);7.4084 (1.97); 7.4032 (1.72); 7.3998 (1.7); 7.385 (0.7); 7.3589 (1.41);7.3368 (1.88); 7.3173 (1.39); 7.1739 (0.83); 7.1704 (0.86); 7.1527(1.79); 7.1353 (1.12); 7.1318 (1.06); 6.9096 (1.27); 6.8915 (2.21);6.8728 (1.02); 6.7927 (2.53); 6.7726 (2.28); 5.7542 (1.11); 5.2613(0.49); 5.2466 (1.08); 5.2274 (1.08); 5.213 (0.48); 4.2679 (1.84);4.2559 (3.15); 4.2415 (1.82); 3.3206 (48.83); 3.1342 (16); 3.0049(0.62); 2.9974 (0.88); 2.9893 (1.13); 2.981 (0.87); 2.9732 (0.63);2.9642 (0.34); 2.675 (0.38); 2.6705 (0.51); 2.6658 (0.38); 2.5232(1.39); 2.5055 (63.06); 2.5011 (86.29); 2.4969 (64.79); 2.3323 (0.36);2.3281 (0.5); 2.1894 (0.6); 2.1757 (0.69); 2.1696 (0.51); 2.156 (0.74);2.1399 (0.74); 2.0304 (0.61); 2.0184 (0.69); 1.9969 (0.54); 1.9883(0.86); 1.3979 (1.47); 0.6101 (1.75); 0.4165 (0.89); 0.0078 (0.39);−0.0001 (10.71); −0.0076 (0.41) 253 2.8 ¹H-NMR (399, 9532 MHz, DMSO): δ= 9.0796 (1.17); 9.0621 (1.2); 8.5624 (8.02); 8.2214 (0.93); 8.2105(1.57); 8.1983 (1.03); 7.6978 (2.04); 7.694 (2.19); 7.6778 (2.53); 7.674(2.5); 7.6177 (5.4); 7.6041 (4.04); 7.4523 (0.69); 7.4433 (0.72); 7.4327(1.48); 7.4239 (1.42); 7.4131 (0.92); 7.4041 (0.85); 7.3455 (1.88);7.329 (3.1); 7.3099 (1.5); 7.174 (0.81); 7.1702 (0.85); 7.1526 (1.69);7.1353 (1.08); 7.1317 (1.05); 6.9092 (1.19); 6.8909 (2.03); 6.8721(0.94); 6.793 (2.33); 6.791 (2.35); 6.7726 (2.13); 6.7706 (2.07); 5.2566(0.41); 5.242 (0.94); 5.2229 (0.94); 5.2089 (0.4); 4.2665 (1.65); 4.2545(2.8); 4.2402 (1.64); 3.3211 (41.34); 3.1368 (16); 3.0138 (0.45); 3.0047(0.7); 2.9975 (0.96); 2.9893 (0.98); 2.9811 (0.72); 2.9735 (0.43);2.6703 (0.39); 2.5235 (1.05); 2.51 (22.39); 2.5056 (47.11); 2.501(65.73); 2.4966 (49.19); 2.4922 (23.62); 2.3279 (0.38); 2.1883 (0.57);2.1742 (0.65); 2.1681 (0.49); 2.1546 (0.71); 2.1385 (0.72); 2.0349(0.45); 2.0228 (0.65); 2.0115 (0.58); 2.0017 (0.49); 1.9882 (1.44);1.9759 (0.32); 1.3975 (1.3); 1.175 (0.52); 0.6137 (1.77); 0.5976 (1.39);0.4649 (0.32); 0.4414 (0.56); 0.4091 (1.27); 0.3695 (0.52); 0.0081(0.44); −0.0002 (13.08); −0.0084 (0.42) 254 3.81 ¹H-NMR (399, 9532 MHz,DMSO): δ = 9.0974 (1.83); 9.0773 (1.86); 8.6752 (7.71); 8.3134 (0.64);8.2118 (1.85); 8.2091 (1.97); 8.1907 (2.14); 8.1877 (2.13); 7.7947(1.87); 7.7919 (1.98); 7.777 (2.41); 7.7741 (2.31); 7.6416 (5.47);7.6376 (12.68); 7.632 (5.99); 7.6281 (3.45); 7.6155 (1.99); 7.6126(2.16); 7.5945 (1.52); 7.3629 (1.74); 7.3442 (1.88); 7.1889 (0.84);7.1854 (0.87); 7.1674 (1.81); 7.1502 (1.1); 7.147 (1.07); 6.9334 (1.31);6.9152 (2.18); 6.8988 (1.01); 6.8964 (1.02); 6.8069 (2.45); 6.7867(2.52); 5.2728 (0.51); 5.2582 (1.13); 5.2387 (1.12); 5.2248 (0.5); 4.281(1.89); 4.2694 (3.1); 4.2546 (1.8); 3.3184 (46.33); 3.1217 (16); 3.0207(0.68); 3.0129 (0.98); 3.0047 (1.28); 2.9963 (0.95); 2.9888 (0.68);2.9802 (0.33); 2.6749 (0.85); 2.6706 (1.14); 2.6661 (0.85); 2.5101(68.82); 2.5059 (137.4); 2.5014 (187.25); 2.4971 (140.59); 2.3327 (0.8);2.3283 (1.08); 2.3241 (0.79); 2.2024 (0.56); 2.1881 (0.67); 2.1696(0.74); 2.1535 (0.7); 2.0686 (0.34); 2.0557 (0.71); 2.0447 (0.85);2.0308 (0.51); 2.0226 (0.61); 2.0084 (0.53); 1.398 (3.21); 0.6121(2.33); 0.5962 (2.26); 0.4148 (1.1); 0.4089 (1.1); 0.3834 (1.16); 0.0079(1.22); −0.0002 (28.51); −0.0084 (1.03) 255 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.40), −0.008 (3.66), 0.008 L1): Rt =(2.37), 1.938 (0.67), 2.015 (1.79), 2.073 1.21 min; (1.20), 2.179(0.64), 2.328 (0.62), 2.366 MS (0.70), 2.385 (0.71), 2.669 (0.51), 3.356(ESIpos): (0.75), 3.498 (16.00), 3.893 (0.87), 3.915 m/z = 576 (0.80),4.216 (0.97), 4.238 (0.76), 4.267 [M + H]+ (0.81), 4.625 (0.99), 4.640(1.04), 4.659 (0.92), 5.267 (0.86), 6.791 (1.73), 6.810 (1.94), 6.925(0.82), 6.941 (1.72), 6.959 (1.12), 7.168 (0.89), 7.185 (1.41), 7.202(0.70), 7.394 (1.48), 7.411 (1.37), 7.645 (11.29), 7.673 (1.76), 7.694(1.53), 7.820 (1.92), 7.838 (1.61), 8.342 (1.64), 8.361 (1.56), 8.671(6.40), 9.188 (1.55), 9.208 (1.60). 256 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ 9.12 (Method (d, J = 8.1 Hz, 1H), 8.62 (s, 1H), 8.43 L2): Rt = (d, J =8.7 Hz, 1H), 7.93 (d, J = 9.1 Hz, 3.91 min; 1H), 7.69 (t, J = 1.9 Hz,1H), 7.37- m/z = 560 7.29 (m, 3H), 7.20-7.13 (m, 1H), 6.94- [M + H]+6.87 (m, 1H), 6.79 (dd, J = 8.2.1.0 Hz, 1H), 5.26-5.19 (m 257 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.43), 0.146 (0.47),1.754 (0.43), L1): Rt = 1.862 (3.00), 1.901 (2.89), 1.909 (2.71), 0.71min; 2.031 (4.75), 2.040 (4.61), 2.049 (5.14), MS 2.157 (2.74), 2.171(3.27), 2.186 (2.55), (ESIpos): 2.203 (1.78), 2.327 (0.93), 2.366(0.74), m/z = 502 2.670 (0.93), 2.709 (0.69), 3.038 (0.45), [M + H]+3.165 (1.51), 3210 (0.53), 3.232 (0.51), 3.476 (2.42), 3.502 (4.70),3.528 (2.55), 3.654 (0.43), 3.708 (1.60), 3.732 (3.42), 3.752 (2.34),3.780 (1.22), 3.802 (2.18), 3.820 (2.17), 3.829 (2.57), 3.851 (3.64),3.861 (4.91), 3.875 (4.51), 3.888 (3.51), 3.900 (2.05), 4.169 (4.22),4258 (8.38), 4.267 (9.23), 4.280 (4.38), 4.372 (4.77), 5.035 (5.52),5.201 (1.06), 5.214 (2.86), 5.227 (3.55), 5.235 (3.58), 5.247 (2.92),5.261 (1.17), 6.782 (7.98), 6.801 (8.91), 6.893 (3.82), 6.912 (8.02),6.930 (4.96), 7.145 (4.32), 7.163 (6.95), 7.182 (3.56), 7.211 (2.94),7.216 (2.31), 7.234 (5.55), 7.240 (4.20), 7 258 (3.02), 7.263 (2.33),7.307 (16.00), 7.324 (15.84), 7.361 (1.03), 7.377 (1.64), 7.399 (0.96),7.467 (4.96), 7.486 (7.17), 7.507 (5.81), 7.704 (8.95), 7.722 (7.93),7.742 (0.47), 7.887 (0.48), 7.901 (0.42), 8.134 (12.65), 8.269 (7.33),8.291 (7.25), 8.313 (0.63), 8.394 (1.77), 8.432 (13.03), 8.436 (13.82),8.810 (1.36), 9.046 (5.84), 9.067 (5.58), 12.645 (0.58). 258 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.99), 0.146 (1.21),1.055 (1.10), L6): Rt = 1.243 (0.89), 1.862 (1.56), 1.907 (1.99), 1.25min; 2.038 (4.22), 2.085 (2.63), 2.159 (2.66), MS 2.327 (2.09), 2.366(1.38), 2.669 (2.27), (ESIneg): 2.710 (1.45), 3.509 (1.42), 3.743(1.67), m/z = 523 3.873 (4.19), 4.251 (8.12), 4.394 (3.19), [M − H]−5.059 (2.13), 5.200 (3.33), 5.754 (16.00), 6.776 (5.14), 6.796 (5.68),6.875 (3.87), 6.893 (7.49), 6.912 (4.43), 7.138 (3.69), 7.157 (5.46),7.177 (3.37), 7.289 (6.17), 7.307 (5.53), 7.448 (3.87), 8.132 (3.30),8.325 (3.87), 9.046 (1.53), 12.220 (0.64). 259 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (1.71), −0.008 (15.12), 0.008 L6): Rt =(13.06), 0.146 (1.65), 1.038 (1.12), 1.055 1.24 min; (2.24), 1.073(1.12), 1.236 (0.71), 1.862 MS (3.06), 1.908 (2.82), 2.039 (5.47), 2.085(ESIpos): (3.00), 2.146 (3.35), 2.160 (3.59), 2.180 m/z = 518 (2.88),2.195 (2.53), 2.327 (2.82), 2.332 [M + H]+ (2.06), 2.366 (2.29), 2.523(8.71), 2.669 (2.59), 2.690 (0.53), 2.709 (2.24), 3.509 (2.00), 3.744(2.29), 3.874 (5.88), 4.238 (8.06), 4.253 (10.94), 4.388 (4.47), 5.054(3.29), 5.205 (4.24), 5218 (4.18), 5.754 (16.00), 6.774 (7.12), 6.795(7.59), 6.878 (5.12), 6.896 (10.53), 6.915 (6.06), 7.139 (4.65), 7.157(7.24), 7.177 (3.76), 7.235 (2.47), 7.290 (10.82), 7.309 (9.65), 7.501(2.94), 7.561 (4.94), 8.132 (6.47), 8.337 (6.94), 9.043 (2.35), 12.703(0.71). 260 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm] (Method 1.898(1.49), 1.907 (1.43), 2.003 (1.23), L1): Rt = 2.023 (2.16), 2.034(2.52), 2.054 (2.37), 0.72 min; 2.156 (1.33), 2.170 (1.58), 2.186(1.26), MS 2.202 (0.87), 3.169 (4.19), 3.191 (0.45), (ESIpos): 3.203(0.50), 3.213 (0.51), 3.226 (0.59), m/z = 500 3.305 (1.15), 3.472(1.52), 3.498 (2.71), [M + H]+ 3.524 (1.46), 3.696 (0.91), 3.720 (1.91),3.741 (1.28), 3.776 (0.63), 3.798 (1.12), 3.817 (1.15), 3.826 (1.36),3.841 (1.73), 3.853 (2.81), 3.867 (2.34), 3.881 (1.91), 3.893 (1.16),4.168 (2.20), 4.258 (4.22), 4.266 (4.57), 4.376 (2.54), 5.217 (1.39),5.228 (1.80), 5.248 (1.46), 5.753 (16.00), 6.780 (4.05), 6.800 (4.44),6.892 (1.82), 6.910 (3.93), 6.929 (2.45), 7.143 (2.06), 7.162 (3.40),7.181 (1.72), 7.306 (3.35), 7.325 (3.06), 7.417 (1.77), 7.436 (4.71),7.450 (3.62), 7.469 (5.99), 7.487 (4.73), 7.503 (3.14), 7.521 (4.74),7.540 (2.68), 7.635 (6.07), 7.659 (4.38), 7.677 (3.91), 8.153 (14.28),8.247 (3.60), 8.268 (3.45), 8.421 (6.72), 8.425 (7.54), 8.792 (0.74),9.041 (2.88), 9.062 (2.77). 261 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (1.36), 0.008 (1.23), 1.897 (0.69), L1): Rt = 2.031(1.04), 2.050 (1.12), 2.156 (0.59), 0.75 min; 2.170 (0.71), 2.185(0.60), 3.169 (0.99), MS 3.191 (0.41), 3.203 (0.54), 3212 (0.50),(ESIpos): 3.226 (0.59), 3.305 (1.07), 3.464 (0.73), m/z = 530 3.490(1.25), 3.518 (0.67), 3.712 (0.82), [M + H]+ 3.734 (0.57), 3.790 (0.55),3.814 (16.00), 3.829 (3.10), 3.847 (1.23), 3.861 (1.14), 3.874 (1.02),3.887 (0.52), 4.163 (2.59), 4.258 (1.91), 4.266 (2.12), 4.374 (1.12),5.234 (0.76), 5.245 (0.63), 5.754 (0.64), 6.781 (1.81), 6.799 (2.04),6.893 (0.86), 6.912 (1.84), 6.930 (1.24), 7.025 (1.53), 7.030 (2.93),7.035 (1.95), 7.075 (2.47), 7.079 (2.80), 7.127 (0.40), 7.145 (0.92),7.162 (1.62), 7.183 (2.94), 7.186 (3.43), 7.231 (0.46), 7.307 (1.49),7.326 (1.37), 7.451 (1.09), 7.469 (1.61), 7.490 (1.32), 7.659 (1.99),7.675 (1.69), 8.151 (5.55), 8.239 (1.63), 8.260 (1.58), 8.422 (3.41),8.427 (3.75), 8.793 (0.92), 9.041 (1.50), 9.062 (1.45). 262 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.82), −0.008 (6.72), 0.008L6): Rt = (6.87), 0.146 (0.82), 0.889 (0.41), 1.236 1.28 min; (0.68),1.862 (2.00), 1.904 (2.50), 2.036 MS (4.81), 2.057 (3.23), 2.073 (2.58),2.148 (ESIpos): (2.61), 2.162 (3.02), 2.178 (2.26), 2.196 m/z = 518(1.91), 2.327 (1.88), 2.366 (1.20), 2.523 [M + H]+ (5.70), 2.669 (1.82),2.709 (1.09), 3.524 (2.23), 3.755 (2.17), 3.818 (2.88), 3.885 (3.41),4.175 (1.41), 4.243 (6.72), 4.256 (8.63), 4.379 (4.34), 5.041 (4.81),5.211 (3.38), 5.224 (3.41), 5.754 (2.38), 6.775 (7.63), 6.794 (8.22),6.883 (3.88), 6.899 (8.07), 6.918 (4.81), 7.139 (4.20), 7.156 (6.55),7.174 (3.29), 7.295 (8.04), 7.312 (8.40), 7.326 (3.90), 7.367 (3.20),7.383 (4.29), 7.400 (2.00), 7.487 (2.08), 7.506 (3.58), 7.525 (2.50),7.634 (5.31), 8.133 (16.00), 8.325 (4.08), 8.360 (8.78), 9.040 (2.67),9.057 (2.67), 12.699 (1.38). 263 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (1.65), 0.008 (1.52), 1.234 (0.49), L6): Rt =2.012 (0.66), 2.029 (0.92), 2.045 (0.89), 2.33 min; 2.059 (1.10), 2.075(1.44), 2.091 (1.89), MS 2.105 (1.51), 2.122 (0.75), 2.141 (0.59),(ESIpos): 2.187 (0.65), 2.204 (0.65), 2.223 (0.59), m/z = 576 2.237(0.50), 2.470 (0.58), 2.523 (1.48), [M + H]+ 3.358 (0.47), 3.375 (0.74),3.392 (0.84), 3.410 (0.50), 3.489 (16.00) 3.885 (0.41), 3.901 (0.97),3.922 (0.95), 3.939 (0.41), 4.277 (1.55), 4.291 (2.65), 4.303 (1.60),4.716 (1.07), 4.729 (1.23), 4.737 (1.20), 4.750 (1.01), 5.254 (0.41),5.268 (0.92), 5.288 (0.94), 5.301 (0.42), 5.754 (8.22), 6.784 (1.67),6.804 (1.85), 6.888 (0.85), 6.891 (0.84), 6.906 (1.80), 6.925 (1.08),7.143 (0.86), 7.147 (0.92), 7.164 (1.44), 7.182 (0.72), 7.186 (0.72),7.292 (1.53), 7.311 (1.42), 7.639 (1.85), 7.643 (3.39), 7.648 (8.87),7.652 (4.00), 7.673 (1.82), 7.676 (1.64), 7.694 (1.64), 7.821 (2.01),7.824 (2.06), 7.839 (1.67), 7.842 (1.59), 8.351 (1.69), 8.354 (1.71),8.372 (1.62), 8.375 (1.52), 8.678 (6.32), 9.190 (1.68), 9.210 (1.63).264 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 0.146 (0.40), 1.139(16.00), 1.158 L6): Rt = (15.94), 1.234 (0.94), 1.963 (2 29), 1.974 1.53min; (2.70), 2.061 (3.26), 2.078 (3.19), 2.097 MS (1.79), 2.163 (1.02),2.327 (0.81), 2.670 (ESIpos): (0.80), 2.710 (0.44), 3.615 (2.37), 4.233m/z = 546 (1.49), 4.254 (2.33), 4.262 (2.43), 5.217 [M + H]+ (1.48),5.236 (1.45), 5.754 (5.93), 6.777 (2.79), 6.798 (3.23), 6.902 (1.43),6.921 (2.91), 6.940 (1.74), 7.146 (1.44), 7.166 (2.27), 7.184 (1.15),7.347 (2.34), 7.365 (2.28), 7.641 (4.23), 7.646 (4.54), 7.657 (14.09),7.661 (8.47), 7.678 (2.81), 7.698 (2.23), 7.819 (3.12), 7.837 (2.42),8.297 (2.64), 8.318 (2.50), 8.803 (9.16), 8.970 (2.59), 8.991 (2.51).265 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]: = 9.00 (d, 1H),8.51 (s, 1H), 8.41 L1): Rt = (d, 1H), 8.14 (s, 1H), 7.82 (t, 1H), 7.70-0.89 min; 7.76 (m, 1H), 7.58-7.64 (m, 3H), 7.53 MS (dd, 1H), 7.30 (d,1H), 7.13-7.20 (m, 1H), (ESIpos): 6.86-6.96 (m, 1H), 6.79 (d, 1H),5.19-5.30 m/z = 492 (m, 1H), 4.21-4.33 (m, 2H), 3.48-3.59 [M + H]+ (m,2H), 1.96-2.22 (m, 2H), 1.25 (t, 3H). 266 LC-MS ¹H-NMR (500 MHz,DMSO-d6) δ [ppm]: (Method −0.007 (3.09), 0.006 (1.99), 1.907 (2.42),L1): Rt = 2.028 (0.58), 2.033 (0.60), 2.044 (0.71), 0.91 min; 2.056(0.83), 2.166 (0.52), 2.175 (0.71), MS 2.185 (0.75), 2.193 (0.77), 2.204(0.50), (ESIpos): 2.358 (0.89), 2.361 (1.22), 2.365 (0.93), m/z = 5622.369 (0.58), 2.392 (0.70), 2.407 (0.71), [M + H]+ 2.514 (3.50), 2.518(3.01), 2.522 (2.34), 2.631 (0.87), 2.635 (1.14), 2.639 (0.81), 3.866(0.46), 3.878 (1.06), 3.895 (0.91), 4.183 (0.43), 4.188 (0.44), 4.205(1.12), 4.224 (0.89), 4.229 (0.73), 4.243 (0.75), 4.250 (1.08), 4.262(0.91), 4.277 (0.46), 4.638 (0.83), 4.649 (1.02), 4.654 (1.33), 4.665(1.06), 5.254 (0.54), 5.264 (1.14), 5.280 (1.10), 5.291 (0.50), 6.786(2.22), 6.788 (2.18), 6.802 (2.42), 6.804 (2.32), 6.919 (1.16), 6.921(1.08), 6.933 (2.26), 6.935 (2.11), 6.948 (1.31), 6.950 (1.18), 7.169(1.12), 7.172 (1.16), 7.186 (1.76), 7.200 (0.93), 7.203 (0.89), 7.388(1.80), 7.403 (1.70), 7.629 (1.72), 7.634 (4.02), 7.637 (8.89), 7.639(16.00), 7.642 (4.87), 7.652 (2.18), 7.654 (1.91), 7.669 (1.82), 7.806(2.51), 7.809 (2.42), 7.821 (2.05), 7.823 (1.86), 8.303 (1.86), 8.320(1.72), 8.680 (8.25), 12.586 (0.91). 267 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method 2.068 (1.35), 2.198 (1.21), 2.210 (1.21), L6): Rt =2.220 (1.14), 3.278 (5.85), 3.289 (6.25), 1.85 min; 3.311 (12.56), 3.604(16.00), 4.215 MS (0.92), 4.237 (1.78), 4.265 (2.72), 5.246 (ESIpos):(1.68), 5.263 (1.68), 5.753 (4.55), 6.780 m/z = 530 (2.37), 6.800(2.65), 6.899 (1.40), 6.917 [M + H]+ (2.61), 6.935 (1.60), 7.114 (2.89),7.136 (3.72), 7.164 (2.76), 7.181 (4.24), 7.186 (4.32), 7.355 (2.53),7.374 (2.43), 7.410 (2.28), 7.415 (2.25), 7.432 (2.02), 7.437 (1.87),7.527 (0.74), 7.547 (0.73), 7.582 (0.60), 7.629 (6.11), 7.647 (3.02),7.665 (1.10), 8.224 (2.04), 8.238 (1.98), 8.571 (5.47), 9.139 (2.37),9.159 (2.29). 268 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 0.008(1.66), 2.032 (1.12), 2.040 (1.20), L6): Rt = 2.051 (1.31), 2.057(1.32), 2.067 (1.86), 1.68 min; 2.072 (1.94), 2.082 (1.19), 2.090(0.84), MS 2.178 (0.94), 2.187 (1.30), 2.199 (1.63), (ESIpos): 2.211(1.54), 2.221 (1.49), 2.233 (0.98), m/z = 514 2.242 (0.78), 2.254(0.49), 2.669 (0.48), [M + H]+ 3.233 (0.95), 3.245 (1.65), 3.264 (4.14),3.277 (8.27), 3.290 (9.38), 3.303 (8.05), 3.310 (8.12), 3.608 (4.08),3.694 (1.02), 3.841 (0.90), 3.860 (7.34), 3.871 (12.70), 3.882 (7.04),3.901 (0.86), 4.165 (0.48), 4.175 (0.48), 4.183 (0.53), 4.208 (0.81),4.216 (1.03), 4.236 (2.56), 4.244 (2.08), 4.257 (3.61), 4.267 (3.55),4.274 (2.38), 4.283 (2.35), 4.296 (0.92), 4.302 (0.93), 5.186 (0.41),5.232 (1.10), 5.246 (2.38), 5.265 (2.35), 5.280 (1.03), 5.753 (0.98),6.749 (0.48), 6.780 (4.50), 6.800 (5.03), 6.834 (0.58), 6.854 (0.72),6.871 (0.52), 6.897 (2.22), 6.916 (4.62), 6.934 (2.69), 6.999 (3.38),7.007 (3.89), 7.021 (3.65), 7.029 (3.73), 7.042 (0.46), 7.075 (2.55),7.087 (2.73), 7.098 (4.07), 7.110 (4.00), 7.143 (2.39), 7.147 (2.50),7.164 (4.00), 7.176 (2.61), 7.184 (4.22), 7.197 (3.38), 7.205 (3.28),7219 (1.66), 7.228 (1.63), 7.245 (0.65), 7.265 (0.49), 7.355 (3.98),7.373 (3.68), 7.519 (0.46), 7.540 (0.43), 7.584 (0.65), 7.599 (0.48),7.609 (0.82), 7.615 (2.02), 7.629 (9.79), 7.648 (5.53), 7.666 (1.75),8.217 (3.69), 8.223 (3.68), 8.236 (3.32), 8.242 (3.35), 8.280 (0.46),8.532 (1.30), 8.572 (16.00), 9.118 (0.49), 9.140 (4.50), 9.160 (4.10).269 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.88),−0.008 (8.18), 0.008 L1): Rt = (7.45), 0.146 (0.90), 1.862 (1.33), 1.9010.75 min; (1.64), 2.006 (1.70), 2.026 (2.93), 2.039 MS (3.18), 2.058(1.87), 2.071 (1.25), 2.144 (ESIpos): (1.40), 2.158 (1.62), 2.174(1.40), 2.192 m/z = 530 (1.09), 2.327 (1.27), 2.366 (0.88), 2.669 [M +H]+ (1.35), 2.709 (0.82), 2.988 (0.49), 3.018 (0.82), 3.080 (0.76),3.090 (0.82), 3.120 (0.64), 3.168 (3.38), 3.189 (1.64), 3.199 (1.70),3.212 (1.83), 3.304 (6.01), 3.458 (2.03), 3.487 (2.61), 3.517 (1.76),3.654 (0.60), 3.683 (1.07), 3.692 (1.19), 3.715 (2.54), 3.728 (1.58),3.736 (1.37), 3.767 (0.66), 3.789 (1.35), 3.807 (1.58), 3.831 (1.83),3.847 (3.20), 3.861 (2.56), 3.874 (3.40), 3.888 (1.23), 4.152 (7.55),4.252 (5.35), 4.377 (2.97), 5.035 (0.45), 5.209 (1.89), 5.225 (1.93),5.264 (0.43), 6.772 (4.37), 6.790 (5.03), 6.809 (0.90), 6.878 (2.19),6.897 (4.78), 6.916 (3.30), 6.935 (0.49), 7.094 (6.19), 7.116 (7.26),7.135 (2.60), 7.153 (4.41), 7.161 (6.99), 7.168 (8.02), 7.214 (1.25),7.221 (1.29), 7.289 (3.71), 7.307 (3.41), 7.341 (0.72), 7.361 (0.64),7.384 (4.27), 7.390 (4.02), 7.406 (3.71), 7.412 (3.61), 7.421 (3.04),7.440 (4.06), 7.450 (1.05), 7.460 (3.61), 7.501 (5.07), 7.504 (5.29),7.518 (3.34), 7.659 (1.00), 7.677 (1.58), 8.177 (16.00), 8.233 (4.10),8.254 (3.80), 8.331 (8.27), 8.335 (8.60), 8.688 (2.58), 9.014 (2.13),9.024 (2.44), 9.035 (2.24), 9.045 (2.24), 9.145 (0.62), 9.165 (0.59).270 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.06),0.008 (2.02), 1.862 (0.52), L6): Rt = 1.902 (0.65), 1.991 (0.45), 2.008(0.70), 1.17 min; 2.029 (1.17), 2.041 (1.33), 2.052 (0.81), MS 2.062(0.77), 2.074 (0.49), 2.085 (0.95), (ESIpos): 2.145 (0.64), 2.159(0.70), 2.175 (0.54), m/z = 514 2.194 (0.46), 3.468 (0.59), 3.498(0.87), [M + H]+ 3.528 (0.48), 3.592 (16.00), 3.702 (0.50), 3.722(0.73), 3.738 (0.54), 3.795 (0.43), 3.813 (0.59), 3.833 (0.70), 3.855(1.29), 3.868 (0.86), 3.881 (0.82), 3.893 (0.49), 4.151 (0.44), 4.241(1.65), 4.254 (2.29), 4.378 (1.10), 5.041 (0.99), 5.210 (0.85), 5.224(0.81), 5.753 (5.11), 6.773 (1.87), 6.793 (2.06), 6.877 (0.94), 6.896(1.98), 6.914 (1.21), 6.988 (0.94), 6.995 (1.10), 7.010 (0.97), 7.018(1.04), 7.061 (0.93), 7.072 (1.01), 7.084 (1.51), 7.095 (1.44), 7.136(1.03), 7.156 (2.10), 7.165 (0.92), 7.177 (1.39), 7.186 (1.11), 7.200(0.54), 7.208 (0.52), 7.289 (1.68), 7.307 (1.53), 7.430 (0.89), 7.448(1.57), 7.469 (1.45), 7.511 (1.95), 7.528 (1.16), 8.134 (5.18), 8.235(1.56), 8.256 (1.45), 8.331 (2.76), 8.335 (3.59), 9.027 (0.68), 9.036(0.99), 9.047 (0.75), 9.057 (0.91). 271 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method −0.150 (0.71), −0.008 (7.12), 0.008 L1): Rt = (7.07),0.146 (0.81), 1.157 (4.10), 1.175 0.78 min; (8.25), 1.192 (4.07), 1.234(4.37), 1.258 MS (1.96), 1.298 (1.33), 1.759 (1.96), 1.913 (ESIpos):(1.69), 1.988 (16.00), 2.051 (3.21), 2.153 m/z = 568 (1.72), 2.168(1.96), 2.328 (1.18), 2.366 [M + H]+ (0.83), 2.669 (1.15), 3.482 (1.52),3.509 (3.31), 3.537 (1.72), 3.601 (1.72), 3.749 (2.23), 3.858 (2.43),3.871 (2.40), 3.884 (2.97), 3.898 (2.04), 4.003 (1.13), 4.021 (3.58),4.038 (3.51), 4.056 (1.20), 4.179 (2.43), 4.265 (5.40), 4.372 (2.70),5.035 (4.93), 5.231 (2.18), 5.753 (0.91), 6.782 (5.20), 6.802 (5.72),6.891 (2.33), 6.910 (5.06), 6.928 (3.21), 7.141 (2.50), 7.162 (4.22),7.184 (2.11), 7.304 (4.32), 7.322 (4.02), 7.480 (3.31), 7.499 (4.47),7.519 (3.68), 7.757 (5.37), 7.774 (4.66), 7.854 (7.12), 7.898 (7.95),7.970 (7.83), 8.137 (1.03), 8.299 (3.12), 8.322 (3.07), 8.420 (9.50),8.427 (9.79), 8.804 (0.96), 9.056 (3.41), 9.075 (3.53). 272 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.150 (0.66), −0.008 (6.04), 0.008L1): Rt = (5.39), 0.146 (0.68), 1.902 (1.46), 1.911 0.74 min; (1.34),2.001 (1.38), 2.011 (1.72), 2.032 MS (2.75), 2.042 (2.15), 2.148 (1.40),2.161 (ESIpos): (1.58), 2.177 (1.24), 2.195 (0.96), 2.270 m/z = 532(16.00), 2.327 (0.88), 2.332 (0.72), 2.366 [M + H]+ (0.84), 2.522(2.61), 2.669 (0.86), 2.709 (0.78), 3.209 (0.40), 3.232 (0.44), 3.479(1.26), 3.507 (2.19), 3.537 (1.20), 3.738 (1.70), 3.758 (1.16), 3.790(0.56), 3.813 (1.00), 3.830 (1.10), 3.848 (1.30), 3.857 (1.48), 3.870(2.75), 3.883 (2.11), 3.896 (1.78), 3.909 (1.08), 4.169 (2.17), 4.244(3.65), 4.256 (4.49), 4.374 (2.29), 5.034 (3.53), 5.212 (1.76), 5.225(1.74), 5.233 (1.40), 5.753 (11.87), 6.774 (3.91), 6.793 (4.33), 6.881(2.01), 6.900 (4.21), 6.918 (2.63), 7.135 (2.07), 7.138 (2.15), 7.156(3.47), 7.174 (1.84), 7.177 (1.76), 7.240 (1.90), 7.247 (2.25), 7.254(2.13), 7.261 (2.07), 7.295 (3.59), 7.314 (3.31), 7.405 (2.07), 7.411(2.15), 7.420 (2.31), 7.426 (2.01), 7.458 (2.45), 7.477 (3.53), 7.498(3.05), 7.604 (4.17), 7.621 (3.31), 8.133 (5.33), 8.299 (3.03), 8.321(2.85), 8.361 (7.30), 8.365 (8.02), 8.733 (0.70), 9.030 (2.93), 9.051(2.79). 273 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(2.37), 0.008 (2.35), 0.551 (0.53), L6): Rt = 0.566 (0.84), 0.576(1.24), 0.588 (1.45), 1.74 min; 0.599 (1.08), 0.611 (1.48), 0.622(1.39), MS 0.632 (0.86), 0.646 (0.65), 0.774 (0.62), (ESIpos): 0.784(0.88), 0.791 (1.19), 0.801 (1.30), m/z = 504 0.811 (1.67), 0.817(1.59), 0.828 (1.34), [M + H]+ 0.846 (0.86), 0.855 (0.50), 1.157 (4.26),1.175 (8.61), 1.193 (4.39), 1.988 (16.00), 2.033 (0.49), 2.041 (0.65),2.051 (0.77), 2.059 (0.84), 2.067 (1.09), 2.075 (1.07), 2.086 (1.16),2.108 (0.49), 2.129 (0.92), 2.141 (0.96), 2.150 (0.81), 2.163 (0.50),2.176 (0.40), 2.523 (1.27), 3.074 (1.32), 3.081 (1.31), 4.003 (1.26),4.021 (3.80), 4.038 (3.76), 4.056 (1.22), 4.229 (0.56), 4.237 (0.42),4.248 (1.37), 4.257 (1.41), 4.268 (1.85), 4.276 (1.87), 4.288 (1.35),4.296 (1.55), 4.316 (0.56), 5.210 (0.65), 5.225 (1.45), 5.244 (1.46),5.259 (0.63), 6.783 (2.84), 6.804 (3.11), 6.881 (1.36), 6.884 (1.39),6.900 (2.84), 6.902 (2.84), 6.918 (1.71), 6.921 (1.66), 7.139 (1.38),7.143 (1.48), 7.160 (2.30), 7.178 (1.14), 7.182 (1.14), 7.290 (2.42),7.309 (2.25), 7.495 (2.03), 7.513 (2.65), 7.515 (2.51), 7.534 (2.35),7.593 (1.59), 7.598 (3.85), 7.602 (4.25), 7.614 (14.30), 7.618 (8.44),7.726 (3.30), 7.742 (2.69), 7.744 (2.68), 8.497 (2.63), 8.581 (9.25),8.625 (2.55), 8.644 (2.39), 8.925 (2.56), 8.945 (2.48). 274 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.88), 0.146 (0.84), 2.052(4.40), L1): Rt = 2.066 (4.83), 2.214 (1.52), 2.327 (1.69), 0.87 min;2.367 (1.09), 2.669 (1.57), 2.709 (0.86), MS 3.395 (1.87), 3.910 (1.80),3.929 (1.91), (ESIpos): 4.172 (0.60), 4.289 (4.76), 4.731 (1.76), m/z =562 4.745 (2.27), 4.764 (1.74), 5.301 (1.84), [M + H]+ 5.318 (1.95),6.770 (3.24), 6.790 (3.65), 6.854 (1.59), 6.872 (3.37), 6.890 (2.08),7.129 (1.78), 7.146 (2.92), 7.165 (1.59), 7.303 (3.15), 7.322 (2.98),7.643 (16.00), 7.674 (2.68), 7.808 (3.99), 7.825 (3.00), 8.323 (3.22),8.343 (2.92), 8.686 (8.56), 9.294 (0.92), 12.581 (0.51). 275 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 1.899 (0.93), 2.033 (1.88),2.162 (1.12), L6): Rt = 2.178 (0.96), 2.337 (16.00), 2.669 (0.47), 1.37min; 3.305 (4.05), 3.485 (0.97), 3.512 (1.74), MS 3.538 (0.94), 3.742(1.19), 3.817 (0.74), (ESIpos): 3.849 (0.94), 3.873 (2.10), 3.885(1.33), m/z = 532 3.899 (1.41), 3.911 (0.81), 4.257 (3.03), [M + H]+4.375 (1.62), 5.036 (0.83), 5.212 (1.24), 6.773 (2.99), 6.793 (3.25),6.884 (1.29), 6.902 (2.92), 6.920 (1.71), 7.138 (1.51), 7.157 (4.16),7.174 (3.09), 7.296 (2.55), 7.314 (2.22), 7.418 (2.01), 7.431 (2.00),7.467 (1.65), 7.484 (2.51), 7.506 (2.14), 7.606 (3.17), 7.623 (2.58),8.136 (11.05), 8.306 (2.13), 8.327 (1.99), 8.361 (5.15), 8.365 (5.57),9.029 (2.00), 9.051 (1.92). 276 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ(Method [ppm] = 8.98 (d, 1H), 8.47 (s, 1H), 8.22 L6): Rt = (br d, 1H),8.03 (br s, 1H), 7.74 (d, 1H), 0.80 min; 7.52-7.66 (m, 4H), 7.33 (d,1H), 7.15 MS (t, 1H), 6.90 (t, 1H), 6.78 (d, 1H), 5.18- (ESIpos): 5.33(m, 1H), 4.19-4.33 (m, 2H), m/z = 522 3.80 (br s, 2H), 1.99-2.23 (m,2H). [M + H]+ 277 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (Method (d, J =8.2 Hz, 1H), 8.53 (s, 1H), 8.28 L2): Rt = (m, 1H), 7.78-7.62 (m, 2H),7.51 (m, 2.86 min; 1H), 7.35 (d, J = 7.1 Hz, 1H), 7.25- m/z = 460 7.11(m, 3H), 6.91 (m, 1H), 6.83-6.75 [M + H]+. (m, 1H), 5.24 (q, J = 5.8 Hz,1H), 4.25 (dt, J = 7.8, 4.8 Hz, 2H) 278 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ 9.17 (Method (d, J = 8.1 Hz, 1H), 8.64 (s, 1H), 8.40 L2): Rt = (dd, J= 9.4, 6.3 Hz, 1H), 7.70 (t, J = 9.1 3.64 min; Hz, 1H), 7.65-7.55 (m,1H), 7.36 (d, J = m/z = 520 6.8 Hz, 1H), 7.30-7.21 (m, 2H), 7.20- [M +H]+ 7.13 (m, 1H), 6.95-6.87 (m, 1H), 6.79 (dd, J = 8.2, 279 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 9.08 (Method (d, J = 8.2 Hz, 1H), 8.55 (s, 1H),8.37 L3): Rt = (dd, J = 9.4, 6.3 Hz, 1H), 7.68-7.54 (m, 3.83 min; 2H),7.34 (d, J = 6.8 Hz, 1H), 7.30- m/z = 478 7.20 (m, 2H), 7.20-7.12 (m,1H), 6.94- [M + H]+ 6.87 (m, 1H), 6.79 (dd, J = 8.2, 1.1 Hz, 1H),5.27-5.19 ( 280 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] = 9.19(d, 1H), 8.62 (s, 1H), 8.57 L1): Rt = (s, 1H), 8.34 (dd, 1H), 7.81-7.90(m, 0.89 min; 2H), 7.75 (dd, 1H), 7.47-7.56 (m, 2H), MS 7.36 (d, 1H),7.12-7.21 (m, 1H), 6.87- (ESIpos): 6.97 (m, 1H), 6.79 (d, 1H), 5.20- m/z= 507 5.32 (m, 1H), 4.18-4.33 (m, 2H), 3.89 [M + H]+ (t, 4H), 2.16-2.28(m, 1H), 2.00-2.11 (m, 1H). 281 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (1.22), 0.008 (1.27), 2.023 (0.43), L6): Rt = 2.058(0.74), 2.065 (0.63), 2.129 (0.65), 1.59 min; 2.148 (0.95), 2.159(1.39), 2.178 (1.50), MS 2.197 (0.65), 2.259 (0.60), 2.271 (0.78),(ESIpos): 2.289 (0.71), 2.322 (0.52), 2.327 (0.59), m/z = 576 2.523(1.62), 2.670 (0.57), 3.336 (1.52), [M + H]+ 3.354 (0.97), 3.632 (0.46),3.644 (0.81), 3.656 (0.92), 3.663 (0.86), 3.688 (16.00), 3.711 (1.43),3.729 (0.81), 3.736 (1.08), 3.764 (1.60), 3.783 (1.39), 3.798 (1.66),3.815 (1.41), 3.823 (0.84), 3.840 (0.60), 4.236 (1.01), 4.248 (1.31),4.259 (1.81), 4.273 (1.00), 5.212 (0.93), 5.232 (0.97), 5.245 (0.41),5.754 (0.44), 6.784 (1.82), 6.804 (1.98), 6.899 (0.92), 6.915 (1.93),6.934 (1.14), 7.149 (0.92), 7.153 (0.95), 7.170 (1.52), 7.187 (0.76),7.334 (1.55), 7.352 (1.44), 7.548 (1.35), 7.566 (1.81), 7.569 (1.62),7.587 (1.49), 7.625 (12.56), 7.756 (2.12), 7.771 (1.68), 7.774 (1.70),8.265 (1.73), 8.287 (1.54), 8.530 (5.88), 9.104 (1.73), 9.124 (1.66).282 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (0.90),0.008 (1.01), 1.356 (0.76), L6): Rt = 2.020 (0.41), 2.030 (0.40), 2.056(0.64), 1.57 min; 2.064 (0.53), 2.115 (0.57), 2.134 (0.66), MS 2.146(0.97), 2.164 (1.20), 2.184 (0.89), (ESIpos): 2.196 (0.51), 2.261(0.56), 2.273 (0.71), m/z = 576 2.280 (0.50), 2.292 (0.68), 2.323(0.44), [M + H]+ 2.327 (0.41), 2.523 (1.03), 3.333 (1.42), 3.352 (0.88),3.653 (0.41), 3.665 (0.84), 3.684 (16.00), 3.702 (0.75), 3.721 (1.33),3.739 (0.72), 3.745 (0.78), 3.776 (2.18), 3.779 (2.21), 3.797 (2.25),4.241 (0.94), 4.250 (1.38), 4.261 (1.78), 5.218 (0.84), 5.238 (0.83),5.754 (1.01), 6.784 (1.63), 6.804 (1.77), 6.895 (0.78), 6.897 (0.81),6.915 (1.64), 6.932 (0.96), 6.934 (0.96), 7.147 (0.79), 7.151 (0.87),7.168 (1.32), 7.186 (0.66), 7.190 (0.67), 7.328 (1.35), 7.345 (1.25),7.544 (1.16), 7.562 (1.51), 7.566 (1.48), 7.584 (1.38), 7.624 (12.39),7.752 (1.74), 7.755 (1.89), 7.770 (1.51), 7.772 (1.51), 8.250 (1.50),8.253 (1.57), 8.271 (1.41), 8.274 (1.38), 8.524 (5.96), 9.102 (1.54),9.123 (1.50). 283 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] =9.05 (d, 1H), 8.44 (s, 1H), 8.29 L6): Rt = (d, 1H), 7.71 (d, 1H),7.57-7.64 (m, 0.81 min; 3H), 7.44-7.52 (m, 1H), 7.32 (d, 1H), MS7.11-7.20 (m, 1H), 6.87-6.95 (m, (ESIpos): 1H), 6.79 (d, 1H), 5.18-5.28(m, 1H), m/z = 534 5.03 (d, 1H), 4.36 (br s, 1H), 4.27 (br t, [M + H]+2H), 3.79-3.93 (m, 2H), 3.68-3.79 (m, 1H), 3.49 (br d, 1H), 2.12-2.24(m, 1H), 1.97-2.10 (m, 2H), 1.89 (br d, 1H). 284 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ (Method [ppm] = 9.05 (d, 1H), 8.43 (s, 1H), 8.29 L6): Rt =(d, 1H), 7.72 (d, 1H), 7.57-7.65 (m, 0.82 min; 3H), 7.45-7.51 (m, 1H),7.32 (d, 1H), MS 7.17 (t, 1H), 6.92 (t, 1H), 6.79 (d, 1H), (ESIpos):5.22 (br d, 1H), 5.03 (d, 1H), 4.37 (br s, m/z = 534 1H), 4.20-4.31 (m,2H), 3.68-3.91 [M + H]+ (m, 3H), 3.51 (br d, 1H), 2.18 (br dd, 1H), 2.03(br dd, 2H), 1.91 (br s, 1H). 285 4.62 ¹H-NMR (399, 9532 MHz, DMSO): δ =9.2548 (2.04); 9.2345 (2.1); 8.7855 (7.26); 8.3664 (2.02); 8.3479(2.11); 8.3453 (2.18); 7.8787 (1.74); 7.8758 (1.94); 7.861 (2.47);7.8581 (2.48); 7.7622 (1.94); 7.7414 (2.32); 7.7231 (1.43); 7.6547 (16);7.377 (1.84); 7.3585 (1.98); 7.2033 (0.85); 7.1998 (0.91); 7.1823(1.91); 7.1646 (1.15); 7.1615 (1.18); 6.9343 (1.34); 6.9157 (2.31);6.8969 (1.1); 6.8176 (2.6); 6.7972 (2.33); 5.7568 (1.47); 5.3034 (0.53);5.2897 (1.2); 5.2703 (1.21); 5.2561 (0.53); 4.2926 (1.27); 4.2792(2.34); 4.2671 (1.8); 4.2581 (1.3); 4.2376 (0.33); 4.0706 (0.7); 4.0524(2.63); 4.0345 (4.44); 4.0171 (4.89); 3.9996 (4.19); 3.9816 (2.38);3.9627 (0.67); 3.6304 (3.62); 3.6065 (3.63); 3.3187 (31.43); 3.1462(13.89); 2.6701 (0.58); 2.6659 (0.46); 2.5055 (77.14); 2.5012 (101.26);2.4969 (75.96); 2.3321 (0.47); 2.3281 (0.61); 2.3241 (0.48); 2.2488(0.44); 2.2418 (0.43); 2.2281 (0.71); 2.2163 (0.79); 2.2064 (0.75);2.1941 (0.66); 2.1845 (0.36); 2.0978 (0.77); 2.0895 (0.89); 2.078(0.63); 2.0643 (0.6); 2.0543 (0.57); 1.9886 (5.88); 1.3664 (0.32);1.2071 (5.79); 1.1896 (12.06); 1.1762 (7.45); 1.1746 (7.59); 1.1724(7.64); 1.1593 (11.84); 1.1417 (5.55); 0.0079 (0.56); −0.0002 (11.57)286 LC-MS ¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: (Method 0.226 (1.29), 0.233(4.30), 0.237 (4.63), L1): Rt = 0.239 (4.52), 0.243 (4.88), 0.249(1.40), 0.71 min; 0.340 (1.52), 0.346 (4.07), 0.350 (4.50), MS 0.357(4.85), 0.360 (3.44), 0.368 (1.04), (ESIpos): 1.356 (1.85), 2.038(0.54), 2.043 (0.74), m/z = 547 2.048 (0.90), 2.055 (1.09), 2.058(1.29), [M + H]+ 2.064 (1.93), 2.069 (2.31), 2.075 (2.90), 2.080 (1.94),2.085 (1.35), 2.091 (0.59), 2.138 (0.52), 2.147 (0.75), 2.153 (0.91),2.160 (1.03), 2.166 (0.97), 2.175 (0.71), 2.183 (0.72), 2.430 (0.61),2.875 (2.56), 2.886 (5.07), 2.896 (2.59), 3.568 (1.55), 3.578 (3.52),3.587 (3.45), 3.597 (1.35), 4.235 (0.44), 4.240 (0.64), 4.246 (0.51),4.253 (1.67), 4.259 (1.50), 4.267 (2.05), 4.272 (2.07), 4.280 (1.42),4.285 (1.84), 4.291 (0.49), 4.299 (0.60), 4.304 (0.43), 5.243 (0.77),5.253 (1.54), 5266 (1.49), 5.276 (0.69), 6.785 (2.94), 6.787 (3.06),6.799 (3.15), 6.801 (3.19), 6.884 (1.60), 6.886 (1.58), 6.897 (3.02),6.899 (2.96), 6.909 (1.78), 6.911 (1.69), 7.149 (1.45), 7.151 (1.48),7.163 (2.43), 7.174 (1.26), 7.177 (1.19), 7.299 (2.47), 7.312 (2.33),7.525 (2.41), 7.537 (2.93), 7.539 (2.68), 7.552 (2.48), 7.603 (2.71),7.606 (5.93), 7.609 (4.64), 7.625 (16.00), 7.628 (11.38), 7.728 (0.51),7.731 (0.49), 7.740 (3.43), 7.741 (3.45), 7.751 (2.98), 7.753 (2.90),7.908 (1.67), 8.353 (2.70), 8.354 (2.72), 8.367 (2.61), 8.369 (2.48),8.549 (9.74), 8.991 (2.87), 9.004 (2.73). 287 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.52), 0.146 (0.53), 1.883 (0.77),L1): Rt = 1.896 (0.94), 1.912 (1.02), 1.927 (1.11), 0.98 min; 1.943(1.13), 1.961 (0.80), 1.971 (1.04), MS 1.990 (1.32), 2.009 (0.93), 2.061(1.59), (ESIpos): 2.074 (1.40), 2.084 (1.11), 2.098 (1.33), m/z = 5482.109 (1.05), 2.191 (2.00), 2.202 (1.93), [M + H]+ 2.226 (1.16), 2.240(0.86), 2.327 (0.57), 2.366 (0.54), 2.669 (0.58), 2.710 (0.53), 3.225(0.66), 3.239 (1.63), 3.252 (3.85), 3.266 (3.91), 3.279 (2.86), 3.800(0.70), 3.818 (1.59), 3.838 (1.38), 3.857 (0.53), 4279 (3.25), 4.293(5.39), 4.304 (3.56), 4.768 (1.59), 4.782 (3.24), 4.795 (1.56), 5.260(0.71), 5.274 (1.51), 5.293 (1.51), 5.308 (0.71), 6.778 (2.68), 6.798(3.02), 6.875 (1.45), 6.893 p.03), 6.912 (1.75), 7.138 (1.46), 7.156(2.35), 7.176 (1.18), 7.292 (2.47), 7.310 (2.24), 7.600 (1.83), 7.621(2.91), 7.638 (16.00), 7.787 (3.16), 7.804 (2.53), 8.227 (2.56), 8.249(2.35), 8.638 (8.70), 9.180 (2.48), 9.201 (2.46). 288 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.41), −0.008 (3.63), 0.008 L1):Rt = (3.20), 0.146 (0.42), 0.853 (0.41), 1.235 0.99 min; (1.98), 1.571(1.78), 1.770 (0.57), 1.783 MS (0.70), 1.800 (0.80), 1.813 (0.68), 1.832(ESIpos): (0.43), 1.896 (0.87), 1.916 (1.53), 1.934 m/z = 548 (1.55),1.951 (0.86), 1.997 (0.58), 2.004 [M + H]+ (0.58), 2.018 (0.64), 2.032(0.84), 2.105 (0.65), 2.117 (0.95), 2.135 (0.76), 2.149 (0.82), 2.172(0.84), 2.185 (0.78), 2.193 (0.74), 2.206 (0.55), 2.327 (0.80), 2.366(0.49), 2.523 (2.44), 2.665 (0.62), 2.669 (0.80), 2.709 (0.47), 3.168(2.40), 3.202 (3.42), 3.235 (0.84), 3.730 (0.53), 3.748 (1.27), 3.769(1.21), 3.787 (0.48), 4.172 (0.78), 4.196 (1.49), 4.202 (1.69), 4.217(1.98), 4.233 (1.24), 4.246 (1.34), 4.252 (1.02), 4.262 (1.06), 4.273(0.58), 4.281 (0.53), 4.775 (0.76), 5.232 (0.50), 5.246 (1.11), 5.266(1.12), 5.280 (0.50), 6.792 (2.30), 6.813 (2.51), 6.929 (1.14), 6.946(2.23), 6.964 (1.27), 7.169 (1.12), 7.173 (1.19), 7.190 (1.80), 7.208(0.87), 7.409 (1.87), 7.427 (1.76), 7.603 (1.59), 7.622 (2.28), 7.625(2.41), 7.637 (16.00), 7.651 (0.76), 7.789 (2.46), 7.804 (1.99), 8.208(1.97), 8.227 (1.82), 8.554 (0.70), 8.654 (8.22), 9.267 (1.92), 9.288(1.85). 289 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149(0.41), 0.853 (0.82), 0.936 14.10), L4): Rt = (0.967 (12.05), 0.979(4.08), 1.010 2.19 min; (0.93), 1.091 (4.11), 1.112 (3.92), 1.128 MS(1.36), 1.141 (1.26), 1.209 (11.78), 1226 (ESIneg): (11.85), 1257(0.62), 1.863 (0.62), 2.038 m/z = 545 (2.45), 2.070 (3.11), 2.086(2.26), 2.124 [M − H]− (1.91), 2.137 (1.96), 2.328 (0.85), 2.366 (0.73),2.524 (1.17), 2.670 (0.58), 2.711 (3.09), 3.066 (0.92), 3.075 (0.86),4.217 (1.18), 4.236 (2.48), 4.254 (2.47), 4.264 (2.19), 4.277 (2.14),4.296 (2.20), 4.323 (1.05), 5.256 (1.20), 5.271 (2.47), 5.288 (2.36),5.754 (6.01), 6.779 (4.19), 6.800 (4.70), 6.850 (1.07), 6.869 (3.08),6.886 (3.51), 6.904 (1.82), 6.921 (0.41), 7.137 (2.50), 7.155 (4.01),7.173 (2.04), 7.246 (2.37), 7.268 (3.62), 7.289 (1.98), 7.527 (2.12),7.546 (3.59), 7.566 (2.59), 7.595 (5.35), 7.599 (4.71), 7.629 (16.00),7.633 (13.65), 7.755 (4.31), 7.772 (3.86), 8.153 (1.08), 8.195 (5.33),8.334 (0.71), 8.562 (0.74), 8.585 (0.69), 8.632 (2.97), 8.640 (2.11),8.653 (2.92), 8.664 (5.42), 8.676 (5.87), 8.916 (1.70), 8.935 (3.21),8.955 (1.84), 8.981 (0.70), 9.001 (0.72), 9.015 (0.69), 9.035 (0.60),9.091 (0.68), 9.148 (0.75). 290 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.149 (1.02), −0.008 (8.92), 0.008 L6): Rt = (8.60), 0.146(1.00), 1.135 (7.45), 1.150 2.50 min; (7.45), 2.092 (0.86), 2.210(0.77), 2.222 MS (0.70), 2.232 (0.75), 2.327 (1.38), 2.366 (ESIpos):(0.75), 2.522 (3.76), 2.669 (1.31), 2.709 m/z = 548 (0.68), 3.011(0.88), 3.040 (1.40), 3.065 [M + H]+ (1.22), 3.171 (0.86), 3.203 (2.49),3.237 (1.13), 3.271 (0.95), 3.882 (0.86), 3.904 (1.86), 3.928 (2.90),4.252 (1.18), 4.260 (1.02), 4.272 (1.81), 4.281 (1.77), 4.297 (0.97),5.264 (1.11), 5.285 (1.13), 5.754 (6.81), 6.791 (2.20), 6.811 (2.42),6.898 (1.09), 6.916 (2.17), 6.932 (1.24), 7.158 (1.11), 7.175 (1.77),7.193 (0.88), 7.373 (1.83), 7.390 (1.67), 7.639 (16.00), 7.682 (1.45),7.700 (2.08), 7.720 (1.88), 7.832 (2.51), 7.847 (1.92), 8.269 (2.08),8.287 (1.92), 8.703 (7.92), 9.162 (1.99), 9.182 (1.90). 291 LC-MS ¹H-NMR(600 MHz, DMSO-d6) δ [ppm]: (Method 0.005 (0.51), 1.849 (0.72), 1.904(0.43), L1): Rt = 1.909 (0.44), 2.009 (0.42), 2.029 (0.63), 0.74 min;2.039 (0.75), 2.044 (0.67), 2.050 (0.81), MS 2.054 (0.88), 2.060 (0.72),2.086 (1.13), (ESIneg): 2.161 (0.42), 2.169 (0.75), 2.177 (0.71), m/z =549 2.184 (0.86), 2.191 (0.78), 2.205 (0.57), [M − H]− 2.517 (0.75),2.520 (0.73), 2.523 (0.59), 3.517 (0.55), 3.523 (0.43), 3.529 (0.50),3.553 (0.60), 3.563 (1.79), 3.570 (1.96), 3.578 (0.98), 3.712 (0.61),3.733 (0.80), 3.751 (0.73), 3.758 (0.72), 3.773 (0.86), 3.777 (1.00),3.791 (1.38), 3.794 (1.30), 3.803 (1.20), 3.806 (1.23), 4.147 (0.64),4.191 (0.42), 4.213 (0.68), 4.217 (0.52), 4.233 (0.62), 4.240 (1.21),4.245 (0.85), 4.253 (2.20), 4.259 (2.32), 4.263 (2.48), 4.271 (1.51),4.979 (0.68), 4.998 (0.65), 5.070 (0.63), 5.090 (0.60), 5.216 (0.57),5.226 (1.21), 5.238 (1.18), 5.247 (0.54), 5.761 (0.76), 6.787 (2.54),6.801 (2.68), 6.909 (1.25), 6.922 (2.41), 6.934 (1.36), 7.154 (1.22),7.167 (1.95), 7.180 (1.02), 7.326 (1.05), 7.339 (1.97), 7.351 (1.01),7.504 (1.06), 7.507 (1.14), 7.519 (2.23), 7.531 (1.20), 7.533 (1.22),7.621 (16.00), 7.737 (2.63), 7.739 (2.75), 7.749 (2.42), 7.751 (2.42),8.247 (1.17), 8.261 (2.15), 8.276 (1.14), 8.463 (4.46), 8.474 (4.71),9.093 (1.35), 9.100 (1.40), 9.107 (1.41), 9.114 (1.26). 292 LC-MS ¹H-NMR(600 MHz, DMSO-d6) δ [ppm] (Method 0.005 (0.57), 1.860 (0.51), 1.871(0.77), L1): Rt = 1.882 (0.62), 1.890 (0.44), 1.909 (0.41), 0.92 min;1.923 (0.56), 1.930 (0.52), 1.934 (0.54), MS 1.940 (0.70), 1.946 (0.52),1.954 (0.72), (ESIneg): 1.961 (0.49), 1.974 (0.44), 2.035 (0.45), m/z =546 2.040 (0.47), 2.049 (0.93), 2.060 (0.97), [M − H]− 2.069 (0.59),2.080 (0.42), 2.086 (1.00), 2.383 (0.46), 2.386 (0.48), 2.389 (0.45),2.475 (0.54), 2.482 (0.97), 2.517 (1.22), 2.520 (1.25), 2.523 (0.98),2.846 (0.43), 2.859 (0.55), 2.871 (0.67), 2.888 (0.55), 2.973 (0.59),2.988 (0.60), 3.000 (0.43), 3.307 (0.67), 3.386 (0.42), 3.399 (0.44),3.808 (0.49), 3.822 (0.49), 3.904 (0.48), 3.918 (0.47), 4.649 (0.59),4.659 (0.66), 4.663 (0.57), 4.672 (0.44), 4.757 (0.59), 4.766 (0.67),4.771 (0.55), 4.779 (0.49), 5.535 (0.60), 5.547 (0.59), 5.578 (0.65),5.591 (0.64), 5.761 (4.08), 7.186 (0.77), 7.198 (0.64), 7.207 (0.58),7.219 (1.00), 7.233 (0.76), 7237 (0.74), 7.239 (0.73), 7.244 (1.42),7.248 (0.86), 7.251 (0.95), 7.254 (1.18), 7.258 (1.17), 7275 (0.96),7.286 (0.49), 7.362 (0.89), 7.374 (0.74), 7.450 (0.61), 7.453 (0.66),7.464 (0.59), 7.623 (0.42), 7.636 (0.92), 7.639 (2.00), 7.644 (16.00),7.646 (12.97), 7.651 (1.35), 7.654 (1.10), 7.657 (1.10), 7.659 (0.98),7.665 (0.95), 7.671 (0.88), 7.806 (1.15), 7.809 (1.53), 7.812 (1.33),7.818 (1.12), 7.821 (1.26), 7.824 (0.95), 8.291 (0.84), 8.293 (0.83),8.305 (0.81), 8.308 (0.78), 8.314 (0.95), 8.316 (0.95), 8.328 (0.80),8.330 (0.76), 8.697 (6.20). 293 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.11(Method (d, J = 8.2 Hz, 1H), 8.61 (s, 1H), 8.22 L3): Rt = (dd, J = 8.5,1.4 Hz, 1H), 7.79 (dd, J = 4.24 min; 7.1, 1.4 Hz, 1H), 7.64 (dd, J =8.5, 7.1 m/z = Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.36 484/486 (d, J =6.8 Hz, 1H), 7.29 (d, J = 2.0 Hz, [M + 1]+ 1H), 7.21-7.14 (m, 1H),6.97-6.88 (m, 1H), 6.80 (dd, J = 82, 1.1 Hz, 1H), 5.30-520 (m, 1H),4.34-4.18 (m, 2H), 3.06 (s, 6H), 2.79 (s, 6H), 2.27- 2.14 (m, 1H),2.13-1.97 (m, 1H). 294 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method(d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.19 L3): Rt = (dd, J = 8.5, 1.5 Hz,1H), 7.72 (dd, J = 3.20 min; 7.1, 1.5 Hz, 1H), 7.61 (dd, J = 8.4, 7.1m/z = Hz, 1H), 7.36 (d, J = 6.7 Hz, 1H), 7.22- 501/503 7.12 (m, 1H),6.97-6.88 (m, 1H), [M + 1]+ 6.86-6.76 (m, 3H), 6. 295 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: (Method 1.900 (1.01), 1.909 (0.98), 2.019 (1.52),L1): Rt = 2.030 (1.94), 2.148 (0.92), 2.162 (1.06), 0.74 min; 2.178(0.86), 2.194 (0.65), 2.399 (16.00), MS 3.169 (5.63), 3.232 (0.41),3.305 (3.16), (ESIpos): 3.314 (2.97), 3.479 (0.92), 3.506 (1.78), m/z =532 3.533 (0.99), 3.711 (0.62), 3.734 (1.27), [M + H]+ 3.755 (0.85),3.789 (0.43), 3.811 (0.79), 3.829 (0.80), 3.845 (0.92), 3.856 (1.20),3.866 (2.03), 3.879 (1.33), 3.894 (1.36), 3.905 (0.71), 4.165 (0.98),4.256 (3.16), 4.374 (1.70), 5.034 (0.67), 5.214 (1.23), 5.226 (1.24),6.773 (2.58), 6.793 (2.90), 6.882 (1.30), 6.901 (2.73), 6.919 (1.67),7.135 (1.40), 7.156 (2.32), 7.174 (1.20), 7.296 (4.04), 7.311 (2.43),7.323 (2.78), 7.424 (2.66), 7.441 (2.63), 7.460 (1.52), 7.478 (2.53),7.499 (1.95), 7.614 (2.84), 7.632 (2.37), 8.137 (4.85), 8.291 (2.22),8.313 (2.08), 8.357 (5.32), 9.028 (1.63), 9.032 (1.65), 9.048 (1.65).296 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (1.98),0.008 (2.08), 3.063 L6): Rt = (16.00), 4.243 (0.55), 4.262 (0.79), 4.2701.34 min; (0.88), 4.283 (0.48), 5.248 (0.49), 5.268 MS (0.51), 6.785(1.01), 6.805 (1.09), 6.905 (ESIpos): (0.49), 6.923 (0.99), 6.939(0.58), 7.150 m/z = 424 (0.51), 7.167 (0.80), 7.348 (0.87), 7.366 [M +H]+ (0.87), 7.378 (1.07), 7.396 (0.89), 7.428 (1.31), 7.447 (2.17),7.465 (0.96), 7.574 (2.11), 7.591 (1.75), 7.595 (1.21), 7.614 (0.67),7.632 (1.09), 7.652 (1.07), 7.697 (1.20), 7.701 (1.29), 7.715 (0.80),7.719 (0.73), 8.174 (1.00), 8.177 (1.02), 8.195 (0.93), 8.199 (0.88),8.583 (3.79), 9.068 (0.83), 9.088 (0.78). 297 LC-MS ¹H-NMR (600 MHz,DMSO-d6) δ [ppm]: (Method 0.005 (0.54), 1.175 (0.51), 1.233 (0.88), L1):Rt = 1.945 (0.48), 1.959 (1.35), 1.966 (0.68), 0.84 min; 1.973 (1.44),1.980 (1.50), 1.987 (0.67), MS 1.990 (0.61), 1.994 (1.45), 2.008 (0.53),(ESIpos): 2.086 (2.18), 2.451 (0.53), 2.457 (0.63), m/z = 492 2.464(1.16), 2.470 (1.43), 2.477 (1.47), [M + H]+ 2.485 (1.96), 2.517 (0.87),2.520 (0.88), 2.524 (0.72), 2.822 (0.63), 2.835 (1.18), 2.849 (1.35),2.862 (1.68), 2.875 (0.78), 2.969 (1.03), 2.975 (1.07), 2.984 (1.12),2.989 (1.08), 2.995 (0.85), 3.001 (0.81), 3.010 (0.76), 3.016 (0.67),3.588 (0.86), 3.598 (2.43), 3.602 (2.62), 3.608 (3.14), 3.617 (1.76),3.632 (0.42), 3.652 (3.34), 3.661 (4.14), 3.669 (1.71), 4.909 (0.68),5.519 (0.77), 5.533 (2.21), 5.546 (2.18), 5.559 (0.73), 7.191 (0.82),7.203 (2.41), 7.213 (3.76), 7.216 (3.96), 7.225 (2.72), 7.227 (2.72),7.237 (1.21), 7.262 (3.11), 7.273 (1.90), 7.357 (2.79), 7.369 (2.30),7.526 (2.39), 7.538 (2.98), 7.540 (2.73), 7.552 (2.48), 7.608 (2.68),7.611 (5.84), 7.614 (4.57), 7.628 (15.29), 7.632 (11.06), 7.741 (3.49),7.713 (3.42), 7.753 (3.14), 7.755 (2.91), 8.061 (1.26), 8.137 (16.00),8.392 (2.82), 8.394 (2.80), 8.407 (2.71), 8.573 (9.90), 8.877 (2.88),8.891 (2.74). 298 LC-MS ¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: (Method 0.005(0.41), 1.942 (0.52), 1.957 (1.44), L1): Rt = 1.963 (0.74), 1.970(1.55), 1.977 (1.60), 0.94 min; 1.984 (0.73), 1.991 (1.56), 2.005(0.56), MS 2.450 (0.57), 2.456 (0.67), 2.463 (1.22), (ESIpos): 2.469(1.51), 2.476 (1.48), 2.484 (1.77), m/z = 506 2.517 (0.76), 2.520(0.73), 2.523 (0.57), [M + H]+ 2.826 (0.69), 2.839 (1.33), 2.852 (1.51),2.866 (1.87), 2.879 (0.87), 2.972 (1.15), 2.978 (1.19), 2.987 (1.24),2.993 (1.19), 2.999 (0.94), 3.004 (0.89), 3.013 (0.85), 3.019 (0.75),3.338 (3.68), 3.398 (0.51), 3.558 (0.53), 3.568 (2.60), 3.576 (6.35),3.585 (4.12), 3.684 (1.95), 3.692 (4.19), 3.701 (3.62), 3.710 (1.33),5.515 (0.84), 5.528 (2.43), 5.541 (2.41), 5.555 (0.80), 7.195 (0.86),7.207 (2.64), 7.216 (3.91), 7.219 (4.26), 7.228 (2.98), 7.230 (2.98),7.240 (1.27), 7.265 (3.39), 7.276 (2.07), 7.355 (2.95), 7.366 (2.41),7.533 (1.96), 7.545 (2.81), 7.559 (2.13), 7.613 (4.94), 7.617 (4.00),7.629 (15.00), 7.632 (10.79), 7.748 (3.54), 7.760 (3.14), 8.100 (1.02),8.136 (6.62), 8.382 (2.78), 8.396 (2.64), 8.586 (8.69), 8.913 (2.35),8.927 (2.27). 299 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm] =11.89 (d, 1H), 8.62 (s, 1H), L6): Rt = 8.16 (d, 1H), 7.70 (d, 1H),7.58-7.66 1.72 min; (m, 3H), 7.50-7.58 (m, 1H), 7.10-7.30 MS (m, 4H),5.51-5.65 (m, 1H), 4.70 (br (ESIpos): d, 1H), 3.95 (br d, 1H), 3.17 (brs, 1H), m/z = 546 2.76-2.99 (m, 2H), 2.30-2.43 (m, 3H), [M + H]+1.88-2.08 (m, 4H). 300 2.6 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]:(Method 2.060 (0.42), 2.066 (0.45), 2.075 (0.47), L1): Rt = 2.088(0.65), 2.094 (0.56), 2.183 (0.44), 1.14 min; 2.193 (0.60), 2.203(0.58), 2.210 (0.55), MS 2.443 (1.65), 2.460 (1.72), 3.126 (0.42),(ESIpos): 3.139 (0.95), 3.155 (0.91), 3.168 (0.40), m/z = 546 3.453(1.32), 3.468 (1.45), 3.473 (1.52), [M + H]+ 3.487 (1.39), 3.880 (1.72),3.887 (1.73), 3.902 (1.54), 3.909 (1.48), 4.231 (0.98), 4.237 (0.78),4.247 (1.45), 4.254 (1.38), 4.268 (0.84), 4.653 (1.89), 4.662 (1.90),5.254 (0.43), 5.266 (0.90), 5.281 (0.89), 6.781 (1.78), 6.797 (1.91),6.891 (0.89), 6.906 (1.77), 6.921 (0.96), 7.149 (0.84), 7.152 (0.86),7.166 (1.42), 7.180 (0.70), 7.389 (1.48), 7.403 (1.38), 7.651 (16.00),7.694 (1.17), 7.708 (1.63), 7.725 (1.38), 7.846 (1.88), 7.859 (1.51),8.297 (1.59), 8.313 (1.46), 8.833 (5.84), 9.232 (1.60), 9.248 (1.53).301 3.3 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 0.006 (0.68),2.065 (0.46), 2.072 (0.53), L1): Rt = 2.084 (0.50), 2.093 (0.68), 2.099(0.58), 1.21 min; 2.106 (0.41), 2.204 (0.47), 2.213 (0.62), MS 2.222(0.62), 2.230 (0.60), 2.518 (0.74), (ESIpos): 3.356 (1.31), 3.379(1.39), 3.420 (1.28), m/z = 576 3.443 (1.40), 3.759 (0.97), 3.785(1.89), [M + H]+ 3.799 (2.05), 3.813 (2.09), 3.819 (1.80), 4.030 (0.93),4.054 (2.69), 4.066 (2.67), 4.084 (2.39), 4.108 (0.98), 4.252 (1.06),4.258 (0.86), 4.268 (1.59), 4.275 (1.59), 4.288 (0.92), 5.257 (0.45),5.269 (0.98), 5.284 (0.95), 5.295 (0.42), 6.789 (1.89), 6.805 (2.04),6.916 (0.91), 6.931 (1.88), 6.946 (1.06), 7.155 (0.89), 7.158 (0.91),7.172 (1.53), 7.186 (0.73), 7.396 (1.60), 7.410 (1.49), 7.641 (16.00),7.674 (1.24), 7.688 (1.77), 7.705 (1.45), 7.813 (1.96), 7.815 (1.98),7.827 (1.59), 8.614 (1.68), 8.631 (1.59), 8.696 (5.91), 9.169 (1.74),9.186 (1.68). 302 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 0.006(1.48), 1.977 (2.45), 1.985 (3.20), L1): Rt = 2.061 (0.94), 2.067(1.00), 2.073 (1.28), 1.32 min; 2.089 (1.37), 2.094 (1.18), 2.101(0.84), MS 2.107 (0.62), 2.196 (0.68), 2.205 (1.01), (ESIpos): 2.212(1.42), 2.222 (1.44), 2.230 (1.70), m/z = 560 2.240 (1.49), 2.252(3.88), 2.271 (3.21), [M + H]+ 2.292 (0.43), 2.361 (0.50), 2.518 (1.55),2.522 (1.14), 2.635 (0.56), 2.976 (2.42), 2.998 (2.58), 3.014 (2.43),3.037 (2.48), 3.530 (3.55), 3.548 (2.59), 3.554 (3.28), 4.225 (0.63),4.230 (0.76), 4.247 (2.09), 4.253 (1.54), 4.264 (1.81), 4.271 (1.84),4.281 (1.90), 4.287 (1.63), 4294 (1.74), 4.303 (0.69), 4.309 (0.76),4.316 (0.55), 4.414 (3.03), 5.247 (0.90), 5.259 (1.92), 5.274 (1.85),5.285 (0.82), 6.790 (3.65), 6.806 (3.88), 6.922 (1.77), 6.936 (3.59),6.951 (2.00), 7.158 (1.76), 7.160 (1.81), 7.174 (2.97), 7.188 (1.47),7.191 (1.38), 7.393 (3.10), 7.408 (2.87), 7.625 (10.72), 7.629 (16.00),7.639 (5.39, 7.643 (5.55), 7.646 (2.39), 7.726 (0.54), 7.729 (0.50),7.740 (2.23), 7.755 (3.44), 7.771 (2.93), 7.838 (3.90), 7.840 (4.07),7.852 (2.90), 8.405 (3.15), 8.420 (2.90), 8.693 (11.68), 9.142 (3.37),9.159 (3.24). 303 3.94 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.1897 (3.07);9.1697 (3.08); 8.6999 (11.32); 8.267 (3.04); 8.2457 (3.34); 8.0999(0.52); 8.0853 (0.45); 7.842 (3.13); 7.8244 (4.12); 7.72 (2.82); 7.6994(3.57); 7.681 (2.24); 7.4668 (0.34); 7.4303 (0.34); 7.3979 (2.99);7.3791 (3.33); 7.3415 (5.08); 7.3244 (4.63); 7.3196 (4.47); 7.3043(1.56); 7.299 (1.58); 7.2806 (2.03); 7.2747 (2.74); 7.2519 (1.45);7.1994 (1.49); 7.1795 (3.11); 7.1614 (1.93); 6.936 (2.19); 6.9174(3.63); 6.8989 (1.79); 6.8126 (4.03); 6.7941 (3.62); 6.5851 (0.63);6.5692 (0.59); 5.2851 (0.87); 5.2712 (1.94); 5.2526 (2.07); 5.238(0.95); 4.3128 (0.7); 4.296 (1.79); 4.2741 (2.81); 4.253 (1.76); 4.2464(2.03); 4.2239 (0.71); 3.9767 (2.68); 3.968 (2.61); 3.3189 (223.97);3.2442 (2.16); 3.2141 (4.55); 3.1853 (2.46); 2.959 (1.92); 2.9418(6.23); 2.9307 (3.17); 2.9237 (3.11); 2.9044 (1.79); 2.8953 (1.74);2.6699 (3.71); 2.5052 (502.23); 2.5009 (661.81); 2.4966 (520.68); 2.3275(3.85); 2.266 (0.88); 2.2232 (1.38); 2.2135 (1.48); 2.2008 (1.46);2.1924 (1.27); 2.0867 (1.57); 2.0741 (1.82); 1.2862 (0.38); 1.2687(0.48); 1.1687 (2.99); 1.1489 (14.24); 1.1439 (16); 1.1337 (15.75);1.1285 (15.3); 0.9796 (0.37); 0.1461 (0.77); −0.0001 (185.99); −0.1498(0.83) 304 4.03 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.1774 (0.67); 9.1576(0.76); 8.5944 (2.4); 8.2724 (1.07); 8.2562 (1.18); 7.9525 (2.49);7.7608 (0.4); 7.7376 (0.43); 7.7214 (0.76); 7.705 (2.49); 7.689 (1.82);7.6851 (2.8); 7.6687 (1.86); 7.6537 (0.93); 7.5047 (0.32); 7.4854(0.91); 7.4653 (1.16); 7.4546 (0.67); 7.4446 (1.44); 7.4361 (1.53);7.4247 (0.93); 7.4155 (0.83); 7.3794 (1.2); 7.3566 (1.16); 7.3429(0.88); 7.3272 (1.2); 7.3088 (0.58); 7.1857 (0.62); 7.1676 (1.13);7.1481 (0.72); 6.9174 (0.63); 6.8992 (0.95); 6.8804 (0.48); 6.8023(1.65); 6.7815 (1.43); 5.2499 (0.69); 5.2313 (0.63); 4.2592 (0.98);4.2328 (0.72); 3.9863 (0.92); 3.3191 (221.03); 3.2639 (0.83); 3.2244(0.64); 3.1788 (0.44); 2.9416 (2.82); 2.9215 (1.53); 2.8905 (16); 2.7311(14.48); 2.6702 (3.3); 2.5232 (7.65); 2.5054 (445.22); 2.5012 (567.66);2.497 (406.38); 2.3321 (2.56); 2.3276 (3.26); 2.2056 (0.52); 2.1956(0.59); 2.1834 (0.61); 2.0737 (0.9); 1.1689 (1.1); 1.1501 (5.7); 1.135(5.9); 0.1463 (0.73); 0.0077 (6.72). −0.0003 (158.9); −0.1492 (0.77) 3054.13 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.0348 (1.54); 9.027 (1.53);9.0145 (1.71); 8.5999 (5.17); 8.5952 (4.9); 8.3156 (0.56); 8.2763(2.51); 8.2726 (2.47); 8.2556 (2.81); 8.2518 (2.69); 7.761 (0.83);7.7408 (1.05); 7.7366 (1.17); 7.7204 (1.9); 7.7118 (3.55); 7.7079(3.89); 7.7027 (4.15); 7.6918 (4.33); 7.6878 (4.41); 7.6822 (4.39);7.6687 (4.22); 7.6652 (4.79); 7.651 (2.14); 7.505 (0.9); 7.4854 (1.99);7.4656 (2.95); 7.4594 (1.58); 7.4449 (3.55); 7.4401 (3.42); 7.4255(3.77); 7.4152 (3.13); 7.3825 (1.69); 7.3796 (1.25); 7.3635 (1.11);7.3418 (1.95); 7.3288 (2.47); 7.3136 (1.38); 7.2798 (1.9); 7.2633(3.48); 7.2506 (1.55); 7.2324 (3.2); 7.2181 (3.48); 7.2031 (2.13);7.1855 (0.81); 7.1649 (0.41); 7.1441 (0.33); 6.5786 (0.32); 5.5633(0.47); 5.5512 (0.67); 5.5336 (1.2); 5.5215 (1.33); 5.5153 (1.19);3.9808 (2.15); 3.6332 (0.34); 3.3942 (0.37); 3.3649 (0.63); 3.3197(538.15); 3.2493 (2.06); 3.221 (1.81); 3.1926 (1); 3.1655 (0.46); 3.0162(0.77); 2.9635 (3.49); 2.9414 (4.71); 2.9076 (2.72); 2.8901 (1.88);2.8843 (2.04); 2.8632 (1.51); 2.8439 (1.23); 2.8236 (0.74); 2.761(0.33); 2.7302 (1.28); 2.7155 (0.39); 2.6747 (4.3); 2.67 (5.87); 2.6656(4.46); 2.6168 (0.41); 2.5905 (0.52); 2.5232 (16.08); 2.5054 (777.81);2.501 (1009.77); 2.4966 (729.53); 2.4266 (0.57); 2.3322 (4.4); 2.3277(5.87); 2.3234 (4.4); 2.2742 (0.35); 2.2675 (0.52); 2.2222 (0.32);2.1718 (0.36); 2.105 (1.65); 2.0945 (1.09); 2.0739 (3); 1.9705 (0.53);1.9506 (1.22); 1.9296 (1.19); 1.919 (1.2); 1.8967 (1.12); 1.8764 (0.43);1.2914 (0.37); 1.2694 (0.4); 1.1687 (2.59); 1.1444 (16); 1.1291 (15.53);1.0966 (0.51); 0.9654 (0.39); 0.1461 (1.27); 0.0078 (11.48); −0.0002(299.28); −0.0082 (14.69); −0.1498 (1.31) 306 4.03 ¹H-NMR (399, 9532MHz, DMSO): δ = 9.0457 (2.18); 9.0244 (2.21); 8.7059 (8.46); 8.3157(0.33); 8.2677 (2.18); 8.2494 (2.31); 8.0868 (0.34); 7.8391 (2.16);7.8242 (2.96); 7.7196 (2.12); 7.6988 (2.55); 7.6804 (1.63); 7.4555(1.75); 7.4412 (2.02); 7.3429 (3.69); 7.3267 (3.62); 7.3056 (1.37);7.2952 (1.61); 7.2766 (4); 726 (2.09); 7.2539 (1.54); 7.2464 (3.22);7.2405 (3.62); 7.2316 (3.27); 7.2236 (2.72); 7.2048 (0.59); 7.1689(0.57); 7.1519 (0.6); 7.1375 (0.42); 6.5782 (0.53); 5.5813 (0.59);5.5623 (1.71); 5.5425 (1.78); 5.5244 (0.59); 3.9738 (1.83); 3.3197(331.29); 3.2386 (1.55); 3.2294 (1.7); 3.2119 (1.9); 3.2003 (1.93);3.0346 (0.53); 3.0265 (0.64); 3.0133 (0.66); 2.9954 (1.02); 2.9859(1.13); 2.9726 (3.04); 2.9417 (5.18); 2.917 (2.47); 2.897 (1.7); 2.8769(1.23); 2.8572 (0.9); 2.8366 (0.65); 2.7309 (0.37); 2.6701 (3.8); 2.5751(0.52); 2.5672 (0.55); 2.5566 (1); 2.5452 (1.54); 2.5053 (506.49); 2.501(657.35); 2.4967 (480.65); 2.355 (0.43); 2.3278 (3.92); 2.2456 (0.33);2.2001 (0.4); 2.1674 (0.46); 2.0952 (0.44); 2.074 (1.44); 1.9927 (0.53);1.9724 (1.13); 1.9617 (0.71); 1.9517 (1.18); 1.9397 (1.1); 1.9195(1.05); 1.8986 (0.43); 1.2999 (0.38); 1.2692 (0.54); 1.1689 (3.6); 1.145(16); 1.1296 (15.96); 1.1004 (0.93); 0.9694 (0.35); 0.1465 (0.88);0.0077 (7.81); −0.0003 (197.85); −0.1495 (0.91) 307 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.2 Hz, 1H), 8.58 (s, 1H), 8.19L3): Rt = (dd, J = 8.5, 1.4 Hz, 1H), 7.74 (dd, J = 4.12 min; 7.1, 1.4Hz, 1H), 7.63 (dd, J = 8.5, 7.1 m/z = Hz, 1H), 7.44 (d, J = 82 Hz, 1H),7.40- 501/503 7.31 (m, 2H), 7.24-7.13 (m, 2H), 6.97- [M + 1]+ 6.88 (m,1H), 6. 308 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.2Hz, 1H), 8.63 (s, 1H), 8.21 L3): Rt = (dd, J = 8.5, 1.3 Hz, 1H), 7.78(dd, J = 4.61 min; 7.1, 1.3 Hz, 1H), 7.63 (s, 3H), 7.37 (d, J = m/z =7.6 Hz, 1H), 722-7.13 (m, 1H), 6.97- 535/537 6.90 (m, 1H), 6.80 (dd, J =8.2, 0.9 Hz, [M + 1]+ 1H), 5.30-5. 309 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ9.10 (Method (d, J = 7.9 Hz, 1H), 8.49 (s, 1H), 8.31, L2): Rt = (d, J =9.4 Hz, 1H), 7.67-7.60 (m, 2H), 3.08 min; 7.44-7.31 (m, 2H), 7.25-7.11(m, 2H), m/z = 564 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.2 [M + H]+1H), 5.23 (q, J = 6.0 Hz, 1H), 4.31- 4.18 (m, 2H), 310 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 9.20 (Method (d, J = 8.1 Hz, 1H), 8.71 (s, 1H), 8.46,L2): Rt = (d, J = 8.9 Hz, 1H), 7.98 (d, J = 9.1 Hz, 3.26 min; 1H), 7.70(t, J = 1.9 Hz, 1H), 7.40- m/z = 7.30 (m, 3H), 7.20-7.13 (m, 1H), 6.95-564/566 6.88 (m, 1H), 6.82-6.76 (m, 1H), (Cl2 5.28-5.20 (m, 1H), 4.32pattern) [M + H]+ 311 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d,J = 8.2 Hz, 1H), 8.61 (s, 1H), 8.17 L3): Rt = (dd, J = 8.5, 1.4 Hz, 1H),7.72 (dd, J = 4.51 min; 7.1, 1.4 Hz, 1H), 7.67-7.58 (m, 2H), m/z = 7.51(dd, J = 8.3, 2.1 Hz, 1H), 7.37 (d, J = 501/503 6.8 Hz, 1H), 7.23 (d, J= 8.4 Hz, 1H), [M + 1]+ 7.21-7.12 (m, 1H 312 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.09 (Method (d, J = 8.2 Hz, 1H), 8.57 (s, 1H), 8.15 L3): Rt= (dd, J = 8.3, 1.6 Hz, 1H), 7.67-7.56 (m, 4.72 min; 2H), 7.36 (d, J =7.5 Hz, 1H), 7.21- m/z = 453 7.10 (m, 2H), 6.96-6.89 (m, 1H), 6.83- [M +1]+ 6.77 (m, 1H), 6.75-6.68 (m, 2H), 6.58-6.52 (m, 1H), 5.6 313 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.16 (Method (d, J = 8.2 Hz, 1H), 8.60 (s,1H), 8.32 L2): Rt = (m, 1H), 7.81-7.68 (m, 2H), 7.58-7.47 3.43 min; (m,1H), 7.37 (d, J = 7.1 Hz, 1H), 7.25- m/z = 502 7.12 (m, 3H), 6.92 (m,1H), 6.82- [M + H]+. 6.76 (m, 1H), 5.26 (q, J = 5.7 Hz, 1H), 4.26 (m,2H), 3.88 (t, 314 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.23 (Method (dd, J= 8.1, 4.6 Hz, 1H), 8.69 (d, J = 4.0 L2): Rt = Hz, 1H), 8.49 (d, J = 9.0Hz, 1H), 8.01 4.05 min; (d, J = 9.0 Hz, 1H), 7.74 (dd, J = 8.1, 1.4 m/z= 602 Hz, 1H), 7.56-7.41 (m, 1H), 7.40- [M + H]+ 7.23 (m, 2H), 7.17 (t,J = 7.7 Hz, 1H), 6.99-6.86 (m, 1 315 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ9.14 (Method (dd, J = 8.1, 4.3 Hz, 1H), 8.60 (d, J = 2.5 L2): Rt = Hz,1H), 8.45 (d, J = 8.5 Hz, 1H), 7.95 3.80 min; (d, J = 9.1 Hz, 1H), 7.72(dd, J = 8.1, 1.5 m/z = 560 Hz, 1H), 7.48-7.40 (m, 1H), 7.37-7.27 [M +H]+ (m, 2H), 7.15 (t, J = 7.7 Hz, 1H), 6.93- 6.87 (m, 1 316 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 9.15 (Method (d, J = 8.1 Hz, 1H), 8.65 (s, 1H),8.20 (d, L3): Rt = J = 2.4 Hz, 1H), 7.87 (d, J = 2.4 Hz, 4.65 min; 1H),7.67 (s, 3H), 7.36 (d, J = 6.7 Hz, m/z = 1H), 7.21-7.14 (m, 1H), 6.92(td, J = 526/528 7.5, 1.2 Hz, 1H), 6.80 (dd, J = 8.2, 1.1 [M + H]+ Hz,1H), 5.28-5.2 317 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (1.21), −0.008 (16.00), 0.008 L6): Rt = (10.22), 0.146 (1.17),1.679 (1.28), 1.768 1.40 min; (1.70), 2.062 (1.06), 2.328 (2.24), 2.367MS (1.03), 2.524 (9.61), 2.671 (2.06), 2.711 (ESIpos): (1.03), 3.648(2.70), 3.664 (3.87), 3.681 m/z = 534 (2.16), 3.818 (1.95), 3.833(2.52), 3.851 [M + H]+ (2.87), 4.252 (2.94), 4.451 (2.50), 5.176 (1.63),5.755 (3.23), 6.818 (1.81), 6.837 (1.70), 6.894 (1.31), 7.193 (1.60),7.294 (1.38), 7.620 (3.48), 7.628 (4.43), 7.672 (1.77), 7.692 (1.42),7.833 (2.98), 7.865 (1.63), 7.970 (6.14), 8.217 (1.67), 8.234 (1.67),8.477 (2.98), 8.881 (10.47), 9.374 (0.85). 318 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.83), −0.008 (6.59), 0.146 L1): Rt =(0.79), 1.156 (0.87), 1.175 (1.80), 1.192 0.81 min; (0.87), 1.235(0.41), 1.660 (1.14), 1.679 MS (1.24), 1.690 (1.49), 1.710 (1.37), 1.903(ESIpos): (1.53), 1.988 (3.52), 1.999 (1.41), 2.012 m/z = 548 (2.20),2.028 (2.14), 2.048 (1.84), 2.058 [M + H]+ (1.57), 2.165 (1.18), 2.181(1.02), 2.197 (0.75), 2.327 (1.16), 2.366 (0.85), 2.393 (1.28), 2.411(1.60), 2.428 (1.39), 2.669 (1.26), 2.709 (0.81), 3.162 (2.53), 3.175(2.69), 3.381 (0.77), 3.408 (1.45), 3.421 (1.62), 3.440 (1.20), 3.467(1.26), 3.483 (3.03), 3.494 (2.47), 3.510 (2.92), 3.528 (1.91), 3.676(1.47), 3.697 (2.53), 3.716 (2.92), 3.724 (2.72), 3.742 (3.19), 3.768(1.62), 4.020 (0.71), 4.038 (0.79), 4.073 (0.66), 4.087 (0.68), 4.172(0.56), 4.254 (4.73), 4.264 (2.90), 4.717 (2.13), 4.729 (4.29), 4.742(2.05), 5.193 (0.81), 5.207 (1.74), 5.226 (1.76), 5.240 (0.87), 5.754(0.50), 6.777 (3.46), 6.797 (3.81), 6.896 (1.66), 6.913 (3.44), 6.931(1.97), 7.144 (1.84), 7.161 (2.90), 7.180 (1.41), 7.319 (2.94), 7.338(2.71), 7.477 (2.16), 7.496 (2.96), 7.517 (2.65), 7.606 (4.71), 7.610(5.82), 7.619 (16.00), 7.623 (9.06), 7.711 (3.79), 7.727 (3.19), 7.873(0.50), 8.267 (3.11), 8.288 (2.92), 8.442 (11.23), 9.024 (3.13), 9.044(3.03). 319 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.062(2.28), 2.197 (2.14), 2.209 (2.13), L6): Rt = 2.218 (2.01), 2.327(0.67), 2.670 (0.64), 1.94 min; 3.876 (16.00), 4.213 (1.25), 4.234(3.18), MS 4.254 (4.91), 4.262 (4.94), 5.244 (2.95), (ESIpos): 5.261(2.87), 6.776 (4.46), 6.796 (4.81), m/z = 500 6.893 (2.44), 6.911(4.65), 6.930 (2.84), [M + H]+ 7.142 (2.94), 7.161 (4.44), 7.179 (2.33),7.351 (7.88), 7.369 (5.89), 7.391 (2.42), 7.416 (5.69), 7.423 (5.81),7.435 (5.30), 7.454 (2.26), 7.537 (3.95), 7.553 (3.04), 7.629 (3.41),7.645 (5.92), 7.671 (3.87), 7.691 (4.59), 7.709 (2.20), 8.265 (4.40),8.285 (4.07), 8.575 (9.62), 9.149 (3.43), 9.168 (3.26). 320 LC-MS ¹H-NMR(500 MHz, DMSO-d6) δ [ppm]: (Method −0.006 (0.66), 0.006 (0.45), 0.992(6.88), L1): Rt = 1.006 (14.64), 1.020 (7.28), 1.175 (0.69), 1.27 min;1.914 (0.43), 1.921 (0.59), 1.928 (1.00), MS 1.935 (0.80), 1.941 (0.98),1.949 (0.81), (ESIpos): 1.963 (0.80), 1.975 (1.05), 1.988 (2.98), m/z =590 1.999 (2.31), 2.015 (2.16), 2.027 (1.48), [M + H]+ 2.044 (1.11),2.050 (0.91), 2.056 (0.64), 2.169 (0.46), 2.176 (0.69), 2.186 (0.98),2.196 (1.00), 2.204 (0.98), 2.214 (0.73), 2.221 (0.48), 2.363 (0.83),2.379 (0.99), 2.392 (0.95), 2.407 (0.54), 2.519 (0.54), 3.335 (0.80),3.347 (1.08), 3.351 (1.20), 3.361 (1.13), 3.375 (0.71), 3.865 (0.61),3.878 (1.35), 3.895 (1.41), 3.903 (1.08), 3.911 (1.18), 3.917 (0.96),3.925 (2.97), 3.936 (3.39), 3.939 (3.31), 3.950 (2.96), 3.957 (0.88),3.964 (0.87), 3.972 (0.69), 4.173 (0.74), 4.201 (0.52), 4206 (0.61),4.223 (1.57), 4.229 (1.11), 4.240 (1.23), 4.246 (1.02), 4.259 (1.03),4.266 (1.36), 4.272 (1.21), 4279 (1.31), 4.288 (0.64), 4.294 (0.66),4.301 (0.49), 4.604 (1.49), 4.615 (1.69), 4.621 (1.65), 4.631 (1.40),5.243 (0.66), 5.254 (1.44), 5.270 (1.42), 5.281 (0.66), 5.754 (0.82),6.792 (2.76), 6.807 (2.92), 6.809 (2.90), 6.925 (1.36), 6.927 (1.41),6.940 (2.72), 6.942 (2.70), 6.955 (1.55), 6.957 (1.49), 7.168 (1.42),7.171 (1.43), 7.185 (2.32), 7.199 (1.13), 7.201 (1.08), 7.397 (2.28),7.411 (2.13), 7.636 (4.40), 7.639 (7.81), 7.642 (16.00), 7.645 (6.46),7.653 (2.33), 7.667 (2.83), 7.670 (2.89), 7.684 (2.31), 7.725 (0.57),7.729 (0.54), 7.819 (2.92), 7.822 (3.03), 7.834 (2.48), 7.836 (2.40),8.343 (2.59), 8.345 (2.59), 8.360 (2.42), 8.362 (2.31), 8.680 (9.87),9.196 (2.58), 9.212 (2.50). 321 3.37 ¹H-NMR (399, 953 MHz, CDCl3) δ =9.1126 (4.72). 9.0958 (4.88). 9.0618 (1.78). 9.0408 (2.05). 8.1159(0.51). 8.1073 (0.56). 8.0994 (0.58). 8.0917 (0.65). 8.0616 (0.48).8.0511 (0.51). 8.0462 (0.52). 8.0366 (0.54). 7.9006 (1.45). 7.881 (1.8).7.8347 (1.41). 7.8147 (2.11). 7.7661 (4.49). 7.761 (4.21). 7.7476(6.54). 7.7434 (5.71). 7.7362 (3.9). 7.7155 (2.95). 7.6982 (1.01).7.5821 (4.98). 7.5623 (5.73). 7.52 (0.37). 7.5044 (1.22). 7.4823 (1.25).7.3467 (2.17). 7.3277 (5.49). 7.3079 (3.8). 7.2837 (3.47). 7.2612(26.99). 7.2424 (6.4). 7.2359 (6.6). 7.2239 (5.17). 7.2163 (7.07).7.1926 (3.1). 7.1696 (0.93). 6.9454 (1.11). 6.9262 (1.9). 6.9079 (0.91).6.8815 (1.42). 6.8676 (6.02). 6.847 (7.37). 6.8332 (1.46). 6.8255(2.03). 6.7513 (0.44). 6.7294 (0.44). 6.6499 (0.51). 6.6309 (0.48).5.463 (0.52). 5.4511 (1.1). 5.4396 (1.55). 5.4277 (2.06). 5.4166 (1.59).5.4055 (1.17). 5.3934 (0.57). 5.3772 (0.45). 5.3618 (0.93). 5.3447(0.94). 5.3304 (0.42). 5.2987 (1.1). 4.345 (1.6). 4.327 (2.15). 4.3161(2.64). 4.2918 (0.9). 4.284 (0.68). 4.2127 (0.88). 4.189 (2.02). 4.1633(2.43). 4.1436 (2.4). 4.1261 (3.47). 4.1083 (3.64). 4.0904 (1.16).3.2611 (13.51). 3.0936 (5.9). 3.0503 (16). 3.0032 (13.51). 2.9661(13.47). 2.9245 (13.29). 2.3901 (0.54). 2.38 (0.86). 2.3661 (1.02).2.3536 (1.63). 2.3427 (1.92). 2.3298 (1.66). 2.316 (1.68). 2.3065(1.38). 2.2921 (0.68). 2.28 (0.49). 22702 (0.36). 2.1215 (1.79). 2.1092(1.54). 2.1028 (1.49). 2.0868 (2). 2.0744 (1.46). 2.0598 (0.73). 2.041(13. 3). 1.5769 (18.97). 1.3654 (0.45). 1.3479 (0.92). 1.3301 (0.51).1.2747 (3.51). 1.2568 (7.17). 1.239 (3.48). −0.0003 (15.15) 322 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (1.57), −0.008(16.00), 0.008 L6): Rt = (12.28), 0.146 (1.64), 1.049 (0.50), 2.087 2.26min; (0.63), 2.327 (3.21), 2.366 (2.46), 2.523 MS (10.58), 2.669 (3.09),2.710 (2.46), 3.611 (ESIpos): (1.20), 3.879 (3.72), 4.269 (1.01), 5.259m/z = 550 (0.69), 6.787 (1.26), 6.807 (1.51), 6.915 [M + H]+ (0.76),6.932 (1.39), 6.950 (0.76), 7.153 (0.76), 7.174 (1.13), 7.374 (1.20),7.391 (1.89), 7.410 (1.26), 7.583 (1.70), 7.596 (2.08), 7.615 (1.70),7.627 (1.95), 7.687 (0.94), 7.706 (1.26), 7.726 (1.32), 7.806 (1.45),7.822 (1.32), 8.270 (1.39), 8.291 (1.20), 8.660 (4.66), 9.158 (1.20),9.180 (1.13). 323 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J =8.2 Hz, 1H), 8.60 (s, 1H), 8.19 L3): Rt = (dd, J = 8.5, 1.3 Hz, 1H),7.73 (dd, J = 2.90 min; 7.1, 1.3 Hz, 1H), 7.62 (dd, J = 8.4, 7.2 m/z =Hz, 1H), 7.36 (d, J = 7.0 Hz, 1H), 543/545 7.22-7.12 (m, 1H), 7.09-6.97(m, 3H), [M + 1]+ 6.97-6.87 (m, 1H), 6. 324 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.08 (Method (d, J = 8.2 Hz, 1H), 8.51 (s, 1H), 8.17 L2): Rt= (dd, J = 8.2, 1.7 Hz, 1H), 7.67-7.50 2.91 min; (m, 2H), 7.34 (d, J =7.1 Hz, 1H), 7.23- m/z = 7.06 (m, 2H), 6.97-6.86 (m, 1H), 6.86- 501/5036.67 (m, 3H), 5.33-5.18 (m, 1H), [M + 1]+ 4.37-4.15 (m, 2H), 3.0 325LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.2 Hz, 1H), 8.63(s, 1H), 8.20 L2): Rt = (dd, J = 8.5, 1.3 Hz, 1H), 7.77 (dd, J = 3.19min; 7.1, 1.3 Hz, 1H), 7.63 (dd, J = 8.4, 7.2 m/z = Hz, 1H), 7.56-7.48(m, 1H), 7.43 (dd, J = 519/521 13.3, 2.0 Hz, 1H), 7.37 (d, J = 6.9 Hz,[M + 1]+ 1H), 7.23-7.13 (m, 1H), 6.98-6.89 (m, 1H), 6.80 (dd, J = 8.2,0.9 Hz, 1H), 5.31-5.20 (m, 1H), 4.35-4.18 (m, 2H), 3.06 (s, 6H), 2.86(d, J = 2.3 Hz, 6H), 2.28-2.13 (m, 1H), 2.13-1.99 (m, 1H). 326 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.01 (Method (d, J = 7.1 Hz, 1H), 8.42 (d, J= 1.6 Hz, L2): Rt = 1H), 8.27 (d, J = 9.4 Hz, 1H), 7.66- 2.86 min; 7.55(m, 2H), 7.43-7.30 (m, 2H), 7.23- m/z = 522 7.12 (m, 2H), 6.89 (t, J =7.4 Hz, 1H), (Cl2 6.78 (d, J = 8.1 Hz, 1H), 5.21 (q, J = 5.9 pattern)Hz, 1H), 4.30-4 [M + H]+ 327 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.01(Method (d, J = 8.2 Hz, 1H), 8.49 (s, 1H), 8.25 L2): Rt = (d, J = 9.5Hz, 1H), 7.62-7.54 (m, 2.96 min; 2H), 7.34 (d, J = 7.0 Hz, 1H), 7.30 (d,J = m/z = 522 1.9 Hz, 2H), 7.19-7.12 (m, 1H), 6.95- (Cl2 6.87 (m, 1H),6.79 (d, J = 8.1 Hz, pattern) 1H), 5.27-5.18 (m, 1H), [M + H]+ 328 3.3¹H-NMR (399, 9532 MHz, DMSO): δ = 9.1516 (1.99); 9.189 (2.07); 8.6957(7.8); 8.3158 (0.74); 8.1756 (2.08); 8.1554 (2.33); 7.8284 (2.07);7.8125 (2.84); 7.6916 (1.99); 7.6725 (2.46); 7.6445 (16); 7.5625 (0.42);7.5064 (0.53); 7.4855 (0.5); 7.489 (0.53); 7.3832 (2.2); 7.3653 (2.8);7.1937 (1.06); 7.1767 (2.08); 7.1581 (1.32); 6.948 (1.5); 6.9294 (2.46);6.9118 (1.23); 6.8712 (0.85); 6.8097 (2.74); 6.79 (2.61); 6.6398 (0.41);6.5791 (0.42); 5.2663 (0.57); 5.253 (1.33); 5.238 (1.23); 5.2205 (0.6);4.872 (0.46); 4.287 (1.27); 4.278 (2.25); 4.2461 (1.37); 4.2259 (0.44);3.538 (1.43); 3.5183 (3.51); 3.503 (2.16); 3.374 (2.24); 3.3585 (3.93);3.3413 (2.21); 3.32 (177.93); 3.1924 (2.23); 3.1748 (4.03); 3.1575(2.8); 3.0637 (15.58); 2.6707 (3.2); 2.5016 (591.34); 2.3283 (3.8);2.2181 (0.84); 2.2067 (0.96); 2.1977 (0.96); 2.1833 (1.83); 2.1627(2.11); 2.1422 (4.09); 2.1222 (2.63); 2.0859 (5); 1.7864 (0.63); 1.7681(1.98); 1.7497 (2.66); 1.787 (1.77); 1.3554 (7.89); 1.2706 (0.49);1.2335 (0.8); 1.1856 (0.8); 1.1692 (2.96); 0.1462 (1.19); 0 (271.12);−0.1493 (1.3) 329 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (0.68), 0.008 (0.56), 1.686 (0.43), L1): Rt = 1.705 (0.40), 1.908(16.00), 1, 98 (0.70), 0.80 min; 1.999 (0.46), 2.012 (0.70), 2.030(0.70), MS 2.047 (0.66), 2.057 (0.44), 2.409 (0.49), (ESIpos): 2.523(0.51), 3.409 (0.50), 3.478 (0.83), m/z = 548 3.496 (0.94), 3.503(0.93), 3.520 (0.72), [M + H]+ 3.689 (0.90), 3.707 (1.31), 3.722 (1.18),3.740 (0.74), 3.746 (0.64), 3.764 (0.47), 4.234 (0.64), 4.242 (0.95),4.254 (1.33), 4.730 (0.48), 5.206 (0.55), 5.225 (0.8), 6.778 (1.01),6.799 (1.13), 6.895 (0.51), 6.912 (1.07), 6.931 (0.64), 7.142 (0.52),7.145 (0.8), 7.163 (0.88), 7.18 (0.43), 7.184 (0.43), 7.322 (0.91),7.341 (0.85), 7.478 (0.75), 7.496 (0.99), 7.499 (0.92), 7.517 (0.89),7.601 (0.47), 7.606 (1.15), 7.610 (1.62), 7.618 (4.75), 7.622 (2.49),7.709 (1.15), 7.712 (1.18), 7.727 (1.01), 7.729 (0.98), 8.139 (0.93),8.258 (0.90), 8261 (0.90), 8.280 (0.91), 8.440 (3.42), 9.025 (1.00),9.046 (0.98). 330 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (1.17), 0.008 (0.88), 2.021 (0.41), L6): Rt = 2.08 (0.47), 2.08(0.52), 2.073 (1.14), 2.01 min; 2.169 (0.52), 2.181 (0.50), 2.191(0.48), MS 2.523 (0.76), 3.082 (16.00), 4.220 (0.74), (ESIpos): 4.226(0.64), 4.240 (1.18), 4.249 (1.20), m/z = 510 4.265 (0.72), 5.213(0.69), 5.229 (0.68), [M + H]+ 5.754 (1.51), 6.772 (l.8), 6.792 (1.55),6.878 (0.73), 6.896 (1.52), 6.915 (0.91), 7.134 (0.75), 7.18 (0.79),7.155 (1.26), 7.173 (0.63), 7.176 (0.61), 7.322 (l.8), 7.337 (1.8), 7.82(0.91), 7.356 (0.87), 7.83 (0.63), 7.366 (0.62), 7.382 (0.84), 7.386(0.81), 7.446 (0.76), 7.459 (0.83), 7.466 (1.28), 7.479 (1.28), 7.485(0.72), 7.499 (0.63), 7.592 (1.03), 7.615 (1.76), 7.68 (1.08), 7.726(l.8), 7.78 (1.40), 7.746 (1.23), 7.750 (1.17), 8.310 (0.92), 8.325(1.02), 8.333 (0.99), 8.349 (0.90), 8.523 (2.23), 8.527 (2.23), 9.057(0.8), 9.061 (0.87), 9.077 (0.8). 331 3.14 ¹H-NMR (399, 9532 MHz, DMSO):δ = 9.1403 (1.94). 9.1288 (2). 9.1208 (2.32). 9.1103 (1.85). 8.6012(10.54). 8.4715 (0.58). 8.3155 (1.57). 8.2143 (2.25). 8.1975 (2.56).8.1729 (1.06). 7.7323 (2.07). 7.7127 (5.31). 7.6894 (10.46). 7.6737(1.95). 7.4635 (1.67). 7.4521 (1.74). 7.4433 (2.94). 7.4332 (2.77).7.4235 (2.08). 7.4143 (1.65). 7.3824 (1.86). 7.3618 (4.63). 7.3428(4.44). 7.3225 (1.63). 7.1895 (1.81). 7.171 (3.64). 7.1535 (2.27).6.9433 (2.6). 6.9255 (4.32). 6.9084 (2.02). 6.8059 (4.77). 6.7848(4.45). 6.5782 (0.9). 5.2488 (1.97). 5.237 (2). 4.725 (1.91). 4.697(7.04). 4.6722 (5.48). 4.6575 (5.6). 4.5955 (1.22). 4.5844 (1.61).4.2921 (2.17). 4.2752 (3.94). 4.2675 (3.64). 4.2552 (2.23). 4.2471(2.41). 4.2281 (0.89). 3.3183 (319.34). 3.2701 (0.87). 3.2496 (0.61).3.1747 (0.71). 3.081 (16). 3.0759 (15.54). 2.9497 (1.08). 2.6703 (8.96).2.5893 (0.63). 2.5051 (1239.6). 2.5012 (1583.24). 2.4971 (1204.24).2.3276 (9.3). 2.2832 (0.88). 22475 (1.34). 2.2286 (1.72). 2.2205 (1.78).2.1313 (0.96). 2.074 (5.92). 2.0168 (0.96). 1.2694 (0.87). 1.169 (4.47).1.0034 (0.71). 0.9887 (0.75). 0.1463 (2.93). −0.0001 (642.47). −0.0792(0.67). −0.1497 (3.13). −3.3083 (0.55) 332 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.57), 0.146 (0.52), 2.063 (1.66),L1): Rt = 2.099 (1.25), 2.118 (1.43), 2.130 (1.93), 0.84 min; 2.149(2.41), 2.167 (1.95), 2.220 (1.77), MS 2.233 (1.79), 2.251 (1.61), 2263(1.00), (ESIpos): 2.327 (1.50), 2.366 (0.82), 2.669 (1.50), m/z = 5622.710 (0.73), 3.195 (1.82), 3.214 (2.75), [M + H]+ 3.232 (2.11), 3.670(1.75), 3.682 (1.88), 3.727 (1.27), 3.745 (3.54), 3.768 (4.92), 3.788(5.88), 3.807 (3.11), 3.831 (1.00), 4.241 (3.47), 4.252 (4.68), 5.212(2.04), 5.232 (2.04), 6.779 (3.36), 6.799 (3.81), 6.894 (1.72), 6.912(3.65), 6.931 (2.13), 7.147 (1.88), 7.164 (3.13), 7.182 (1.54), 7.329(3.36), 7.347 (3.06), 7.522 (2.18), 7.542 (3.36), 7.562 (2.63), 7.623(16.00), 7.742 (3.99), 7.759 (3.43), 8.257 (3.50), 8.277 (3.29), 8.501(9.67), 9.095 (3.34), 9.115 (3.29), 12.559 (0.52). 333 LC-MS ¹H-NMR (400MHz, DMSO-d6) delta (Method [ppm]: 2.092 (0.76), 3.286 (3.16), 4.171L6): Rt = (16.00), 4.267 (1.78), 5.273 (1.01), 6.793 2.56 min; (1.51),6.817 (1.83), 6.912 (0.84), 6.931 MS (1.63), 6.949 (1.01), 7.160 (0.88),7.182 (ESIpos): (1.36), 7.359 (1.40), 7.378 (1.33), 7.703 m/z = 497(1.10), 7.723 (1.64), 7.741 (1.31), 7.843 [M + H]+ (4.97), 7.859 (4.94),7.903 (1.82), 7.917 (1.37), 8.294 (1.60), 8.297 (1.77), 8.315 (1.52),8.816 (5.70), 9.194 (1.47), 9.213 (1.36). 334 LC-MS ¹H-NMR (500 MHz,DMSO-d6) delta (Method [ppm]: −0.007 (4.15), 0.007 (3.67), L7): Rt =1.235 (1.26), 1.395 (7.56), 1.409 (16.00), 2.60 min; 1.423 (7.72), 1.950(1.18), 1.966 (1.28), MS 1.975 (1.34), 1.991 (1.30), 2.522 (1.98),(ESIpos): 2.853 (1.24), 2.869 (1.51), 2.885 (1.92), m/z = 477 2.901(0.85), 2.981 (1.03), 2.989 (1.09), [M + H]+ 2.999 (1.11), 3.006 (1.07),3.013 (0.81), 3.286 (5.84), 4.352 (1.51), 4.354 (1.53), 4.366 (4.56),4.368 (4.83), 4.380 (4.46), 4.383 (4.79), 4.394 (1.38), 4.396 (1.51),5.533 (0.78), 5.549 (2.29), 5.564 (2.27), 5.580 (0.78), 5.754 (0.91),7.227 (2.02), 7.231 (3.49), 7.238 (4.46), 7.245 (4.52), 7.249 (3.34),7.260 (1.11), 7.278 (2.99), 7.290 (1.65), 7.294 (1.20), 7.400 (2.19),7.406 (2.33), 7.417 (2.00), 7.654 (2.35), 7.658 (5.35), 7.661 (4.98),7.674 (15.77), 7.678 (10.55), 7.714 (2.52), 7.729 (3.39), 7.731 (3.32),7.745 (2.97), 7.889 (3.47), 7.891 (3.80), 7.903 (3.01), 7.906 (3.03),8.304 (3.32), 8.307 (3.57), 8.321 (3.16), 8.324 (3.16), 8.842 (11.93),8.998 (2.83), 9.015 (2.77). 335 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta(Method [ppm]: −0.008 (1.09), 0.008 (1.03), L1): Rt = 1.300 (13.37),1.315 (15.22), 1.320 1.42 min; (15.14), 1.335 (13.44), 2.077 (1.40),2.086 MS (1.14), 2.175 (0.96), 2.188 (1.01), 2.198 (ESIpos): (1.11),2.211 (0.97), 3.287 (1.40), 4.251 m/z = 507 (1.94), 4.260 (2.90), 4.271(3.78), 4.279 [M + H]+ (2.28), 4.285 (1.96), 4.831 (0.79), 4.847 (2.11),4.862 (2.86), 4.877 (2.07), 4.892 (0.76), 5.271 (1.74), 5.291 (1.73),5.754 (1.60), 6.792 (2.95), 6.795 (3.21), 6.812 (3.38), 6.815 (3.52),6.905 (1.65), 6.908 (1.68), 6.923 (3.35), 6.926 (3.31), 6.942 (2.06),6.945 (1.96), 7.159 (1.66), 7.163 (1.75), 7.180 (2.64), 7.197 (1.36),7.202 (1.34), 7.352 (2.66), 7.356 (2.66), 7.371 (2.57), 7.375 (2.32),7.648 (1.92), 7.653 (4.51), 7.658 (3.68), 7.680 (16.00), 7.685 (11.73),7.701 (2.83), 7.719 (3.62), 7.722 (3.32), 7.740 (3.41), 7.880 (3.80),7.884 (4.07), 7.898 (3.21), 7.902 (3.13), 8.304 (3.63), 8.308 (3.69),8.325 (3.41), 8.329 (3.23), 8.844 (13.48), 9.131 (3.03), 9.152 (2.95).336 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (3.40),0.008 (3.27), L1): Rt = 1.234 (1.59), 1.255 (13.29), 1.270 (13.33), 1.47min; 1.324 (13.22), 1.339 (13.35), 1.958 MS (1.08), 1.976 (1.27), 1.988(1.33), 2.008 (ESIpos): (1.28), 2.517 (2.28), 2.849 (1.21), 2.869 m/z =491 (1.58), 2.889 (2.03), 2.908 (0.90), 2.981 [M + H]+ (1.12), 2.992(1.19), 3.003 (1.21), 3.013 (1.12), 3.288 (2.34), 4.795 (0.80), 4.810(2.09), 4.825 (2.87), 4.841 (2.06), 4.856 (0.77), 5.539 (2.27), 5.558(2.27), 7.221 (2.05), 7.226 (3.83), 7.234 (4.60), 7.243 (5.51), 7.248(3.90), 7.261 (1.41), 7.266 (1.19), 7.275 (3.08), 7.289 (1.56), 7.297(1.00), 7.402 (2.18), 7.409 (2.34), 7.423 (1.93), 7.651 (2.03), 7.656(4.64), 7.661 (3.85), 7.682 (16.00), 7.687 (11.77), 7.702 (2.80), 7.720(3.59), 7.723 (3.36), 7.741 (3.39), 7.879 (3.80), 7.883 (4.13), 7.897(3.21), 7.901 (3.15), 8.305 (3.55), 8.309 (3.70), 8.326 (3.40), 8.330(3.18), 8.861 (12.80), 8.984 (2.98), 9.004 (2.89). 337 LC-MS ¹H-NMR (400MHz, DMSO-d6) delta (Method [ppm]: −0.008 (3.13), 0.008 (3.33), L1): Rt= 1.233 (0.81), 1.599 (1.35), 1.607 (1.77), 1.54 min; 1.618 (2.67),1.624 (2.67), 1.655 (1.41), MS 1.671 (1.41), 1.685 (1.17), 1.707 (0.97),(ESIpos): 1.760 (1.28), 1.773 (2.47), 1.785 (3.62), m/z = 517 1.791(3.70), 1.799 (3.24), 1.804 (3.14), [M + H]+ 1.813 (3.40), 1.818 (3.25),1.824 (2.52), 1.829 (2.47), 1.852 (1.86), 1.861 (1.79), 1.873 (1.75),1.952 (1.31), 1.963 (0.89), 1.970 (1.48), 1.982 (1.57), 1.990 (0.88),2.002 (1.52), 2.021 (0.70), 2.517 (2.37), 2.845 (1.39), 2.865 (1.83),2.885 (2.35), 2.905 (1.05), 2.979 (1.28), 2.989 (1.38), 3.001 (1.41),3.011 (1.32), 3.018 (0.95), 3.029 (0.85), 3.040 (0.83), 3.288 (1.16),5.212 (1.44), 5.218 (2.09), 5.224 (2.42), 5.229 (2.21), 5.236 (1.36),5.518 (0.92), 5.537 (2.66), 5.556 (2.65), 5.575 (0.92), 5.754 (1.62),7.218 (2.33), 7.223 (4.35), 7.231 (4.99), 7.240 (6.10), 7.245 (4.34),7.258 (1.57), 7.263 (1.32), 7 272 (3.57), 7.287 (1.82), 7.294 (1.20),7.412 (2.53), 7.419 (2.76), 7.433 (2.33), 7.647 (1.83), 7.652 (4.58),7.657 (3.89), 7.676 (16.00), 7.680 (11.73), 7.694 (2.99), 7.712 (3.95),7.715 (3.80), 7.733 (3.62), 7.868 (4.03), 7.871 (4.39), 7.885 (3.41),7.889 (3.40), 8.250 (3.81), 8.254 (4.05), 8.271 (3.65), 8.274 (3.52),8.818 (13.85), 9.049 (3.54), 9.069 (3.47). 338 LC-MS ¹H-NMR (400 MHz,DMSO-d6) delta (Method [ppm]: −0.008 (1.69), 0.008 (1.48), 3.284 L6): Rt= (16.00), 3.722 (1.56), 3.734 (2.60), 3.744 2.62 min; (1.75), 4.270(1.58), 4.419 (0.92), 4.428 MS (1.44), 4.431 (1.39), 4.437 (1.43), 4.439(ESIpos): (1.46), 4.448 (0.90), 6.794 (1.04), 6.797 m/z = 523 (1.09),6.814 (1.20), 6.817 (1.20), 6.921 [M + H]+ (1.21), 6.924 (1.15), 6.940(0.75), 7.181 (0.92), 7.352 (0.93), 7.372 (0.91), 7.658 (1.44), 7.662(1.50), 7.676 (5.94), 7.681 (3.69), 7.721 (0.99), 7.739 (1.31), 7.742(1.17), 7.760 (1.24), 7.895 (1.40), 7.899 (1.44), 7.913 (1.18), 7.916(1.10), 8.335 (1.30), 8.339 (1.31), 8.356 (1.25), 8.360 (1.14), 8.877(4.74), 9.141 (1.07), 9.161 (1.04). 339 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method −0.149 (0.97), −0.008 (8.24), 0.008 L6): Rt = (7.67),0.146 (1.01), 1.147 (0.93), 1.750 2.54 min; (1.59), 1.915 (1.63), 2.075(1.10), 2.204 MS (0.97), 2.366 (1.45), 2.669 (0.79), 2.710 (ESIpos):(1.37), 3.287 (6.79), 3.337 (2.25), 3.366 m/z = 549 (1.90), 3.390(0.97), 3.865 (2.47), 3.895 [M + H]+ (2.20), 4.253 (1.45), 4.282 (2.64),4.748 (1.06), 4.758 (1.45), 5.272 (1.45), 5.292 (1.54), 6.795 (2.69),6.798 (2.87), 6.815 (2.91), 6.818 (3.13), 6.910 (1.41), 6.913 (1.37),6.929 (2.78), 6.932 (2.82), 6.948 (1.72), 6.951 (1.72), 7.165 (1.41),7.169 (1.54), 7.189 (2.12), 7.208 (1.15), 7.387 (2.29), 7.407 (1.98),7.652 (2.12), 7.657 (4.94), 7.661 (4.58), 7.678 (16.00), 7.683 (10.31),7.725 (2.20), 7.742 (3.00), 7.746 (2.82), 7.764 (2.78), 7.894 (3.26),7.898 (3.44), 7.912 (2.69), 7.916 (2.60), 8.366 (3.00), 8.370 (3.09),8.387 (2.78), 8.391 (2.60), 8.852 (11.94), 9.170 (2.51), 9.191 (2.51).340 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 1.233 (1.46), 2.060(1.17), 2.072 (1.22), L6): Rt = 2.096 (1.85), 2.106 (1.52), 2.180(1.45), 2.35 min; 2.200 (1.60), 2.216 (1.38), 2.232 (1.09), MS 2.710(0.59), 3.289 (2.29), 3.770 (2.50), (ESIpos): 3.782 (6.45), 3.794(6.45), 3.807 (2.58), m/z = 509 4.251 (3.09), 4.260 (3.55), 4.268(6.08), [M + H]+ 4.280 (3.73), 4.310 (0.75), 4.322 (1.11), 4.337 (3.05),4.348 (6.79), 4.359 (6.81), 4.370 (2.86), 4.385 (0.96), 5.066 (2.32),5.079 (4.75), 5.093 (2.23), 5.263 (1.21), 5.277 (2.42), 5.296 (2.39),5.311 (1.08), 5.753 (12.22), 6.792 (4.39), 6.812 (4.98), 6.902 (2.47),6.920 (4.70), 6.939 (2.63), 7.160 (2.23), 7.179 (3.73), 7.198 (2.03),7.349 (3.82), 7.366 (3.59), 7.603 (0.66), 7.608 (0.74), 7.648 (2.33),7.653 (5.18), 7.658 (5.13), 7.674 (16.00), 7.679 (12.12), 7.703 (2.84),7.723 (4.62), 7.742 (3.57), 7.885 (3.87), 7.888 (4.97), 7.903 (3.20),7.906 (3.94), 8.442 (3.94), 8.445 (4.43), 8.463 (3.83), 8.466 (4.03),8.845 (14.44), 9.174 (4.04), 9.194 (3.96). 341 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 1.356 (12.14), 1.405 (7.22), 1.423 L6): Rt =(15.61), 1.441 (7.48), 2.073 (1.45), 2.082 2.64 min; (1.17), 2.091(0.93), 2.183 (2.15), 2.192 MS (0.97), 2.203 (0.95), 3.568 (4.88), 4.247(ESIpos): (1.66), 4.256 (2.16), 4.268 (2.79), 4.274 m/z = 493 (2.58),4.283 (1.57), 4.359 (1.14), 4.366 [M + H]+ (1.13), 4.377 (3.75), 4.383(3.69), 4.394 (3.64), 4.401 (3.71), 4.412 (1.11), 4.418 (1.11), 5.274(1.50), 5.294 (1.49), 6.793 (2.69), 6.796 (2.93), 6.814 (3.05), 6.817(3.20), 6.871 (0.97), 6.908 (1.45), 6.911 (1.48), 6.927 (2.96), 6.930(2.93), 6.946 (1.82), 6.949 (1.73), 7.160 (1.45), 7.165 (1.54), 7.182(2.32), 7.199 (1.17), 7.203 (1.14), 7.352 (2.34), 7.372 (2.26), 7.376(2.03), 7.650 (1.93), 7.655 (4.49), 7.659 (4.77), 7.672 (16.00), 7.677(9.62), 7.709 (2.46), 7.727 (3.23), 7.730 (3.00), 7.748 (3.04), 7.888(3.41), 7.891 (3.59), 7.905 (2.88), 7.909 (2.77), 8.301 (3.25), 8.305(3.35), 8.322 (3.10), 8.326 (2.87), 8.833 (12.05), 9.137 (2.57), 9.158(2.52). 342 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm] (Method 0.951(16.00), 1.175 (0.68), 1.783 (0.75), L6): Rt = 1.802 (1.29), 1.820(0.77), 1.988 (1.34), 3.11 min; 4.409 (0.73), 4.414 (0.72), 7.655(0.81), MS 7.659 (0.83), 7.670 (2.53), 7.675 (1.64), (ESIpos): 7.720(0.69), 7.878 (0.71), 8.816 (2.01). m/z = 533 [M + H]+ 343 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.37), 0.008 (1.76), 1.147(1.15), L6): Rt = 1.926 (1.02), 1.944 (1.15), 1.957 (1.15), 2.84 min;1.976 (1.22), 2.366 (1.63), 2.710 (1.69), MS 2.838 (0.95), 2.858 (1.29),2.878 (1.69), (ESIpos): 2.956 (0.88), 2.966 (1.02), 2.979 (1.02), m/z =557 2.987 (1.02), 3.289 (3.66), 5.382 (7.73), [M + H]+ 5.386 (8.00),5.415 (0.75), 5.565 (2.03), 5.584 (1.97), 7.132 (0.88), 7.150 (2.37),7.169 (1.69), 7.204 (1.97), 7.223 (4.00), 7.232 (2.03), 7.242 (1.97),7.252 (1.29), 7.264 (3.53), 7.282 (1.69), 7.318 (2.24), 7.336 (4.81),7.365 (1.76), 7.381 (2.98), 7.400 (2.92), 7.447 (1.15), 7.463 (1.76),7.468 (1.97), 7.483 (2.10), 7.488 (1.29), 7.503 (1.08), 7.661 (1.56),7.666 (3.80), 7.670 (4.95), 7.681 (16.00), 7.686 (9.15), 7.718 (2.51),7.736 (3.19), 7.739 (3.12), 7.757 (3.05), 7.903 (3.39), 7.906 (3.80),7.920 (2.92), 7.924 (2.98), 8.278 (3.12), 8.281 (3.46), 8.299 (3.05),8.303 (2.98), 8.913 (11.73), 9.095 (2.71), 9.115 (2.71). 344 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 1.235 (1.30), 1.935 (1.60),1.954 (1.98), L6): Rt = 1.965 (2.10), 1.986 (1.91), 2.005 (0.73), 2.84min; 2.672 (0.79), 2.711 (0.59), 2.843 (1.62), MS 2.863 (2.27), 2.884(2.82), 2.904 (1.36), (ESIpos): 2.969 (1.94), 2.982 (1.99), 5.450(1.65), m/z = 575 5.478 (7.32), 5.493 (7.42), 5.522 (1.77), [M + H]+5.546 (1.27), 5.563 (3.23), 5.583 (3.15), 5.601 (1.18), 7.146 (1.70),7.164 (4.06), 7.182 (3.27), 7.207 (2.49), 7.224 (4.59), 7.242 (2.89),7.264 (6.36), 7.282 (5.13), 7.311 (1.84), 7.392 (5.56), 7.410 (6.38),7.434 (2.03), 7.473 (1.31), 7.495 (2.55), 7.518 (2.46), 7.540 (1.11),7.665 (7.07), 7.680 (16.00), 7.706 (2.83), 7.724 (4.62 7.744 (2.99),7.898 (4.83), 7.916 (4.01), 8.213 (4.51), 8.234 (4.18), 8.918 (9.86),9.128 (3.96), 9.147 (3.86). 345 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.964 (0.76), 2.524 (1.70), 2.861 (0.81), L6): Rt = 2.881(1.06), 3.288 (1.25), 3.759 (16.00 2.83 min; 5.351 (4.36), 5.356 (4.34),5.573 (1.21), MS 5.593 (1.19), 6.939 (1.06), 6.946 (1.14), (ESIpos):6.963 (1.25), 7.038 (1.56), 7.056 (4.26), m/z = 569 7.160 (1.59), 7.179(1.19), 7.208 (0.94), [M + H]+ 7.226 (1.85), 7.243 (1.17), 7.266 (2.21),7.285 (1.11), 7.316 (1.26), 7.337 (1.99), 7.355 (1.09), 7.392 (1.78),7.410 (1.52), 7.657 (1.23), 7.662 (2.51), 7.666 (2.55), 7.679 (7.30),7.683 (4.89), 7.708 (1.19), 7.726 (1.75), 7.747 (1.41), 7.892 (1.85),7.895 (1.92), 7.910 (1.52), 7.913 (1.46), 8.273 (1.73), 8.277 (1.74),8.294 (1.66), 8.298 (1.55), 8.899 (5.35), 9.092 (1.61), 9.113 (1.58).346 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.897 (1.03), 3.371(1.10), 3.386 (1.01), L6): Rt = 5.457 (1.45), 5.543 (1.27), 5.562(1.29), 1.65 min; 7.232 (1.04), 7.237 (1.87), 7.245 (2.18), MS 7.254(2.72), 7.258 (2.05), 7.284 (1.61), (ESIpos): 7.298 (0.86), 7.431(1.08), 7.438 (1.17), m/z = 518 7.452 (1.00), 7.670 (16.00), 7.720(1.27), [M − 7.738 (1.69), 7.741 (1.59), 7.759 (1.49), HCl + H]+ 7.918(1.80), 7.921 (1.89), 7.936 (1.57), 7.939 (1.51), 8.494 (1.49), 8.515(1.46), 8.867 (5.92), 9.235 (1.48), 9.255 (1.44). 347 LC-MS ¹H-NMR (500MHz, DMSO-d6) δ [ppm]: (METHOD 1.166 (16.00), 2.055 (1.38), 2.069 (2.83L5): Rt = 2.084 (1.40), 2.873 (0.61), 2.889 (0.78), 1.39 min; 3.108(11.26), 4.418 (0.63), 4.433 (1.14), MS 4.447 (0.94), 4.460 (1.14),4.474 (0.60), (ESIpos): 5.544 (0.93), 5.560 (0.92), 7.215 (1.08), m/z =549 7.226 (1.40), 7.230 (1.64), 7.243 (1.31), [M + H]+ 7.257 (0.63),7.273 (1.47), 7.287 (0.74), 7.417 (1.21), 7.432 (1.02), 7.647 (0.90),7.651 (2.01), 7.654 (1.86), 7.670 (4.81), 7.674 (4.24), 7.701 (0.83),7.717 (1.39), 7.732 (0.97), 7.875 (1.18), 7.877 (1.48), 7.889 (1.02),7.891 (1.21), 8.314 (1.14), 8.316 (1.40), 8.331 (1.09), 8.333 (1.27),8.809 (3.64), 9.077 (1.18), 9.093 (1.15). 348 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 1.235 (2.39), 1.331 (1.53), 1.554 (1.87), L6):Rt = 1.570 (3.23), 1.583 (3.23), 1.587 (3.23), 3.09 min; 1.810 (1.44),1.948 (0.98), 1.967 (1.15), MS 1.978 (1.21), 1.998 (1.12), 2.327 (0.78),(ESIpos): 2.366 (1.18), 2.391 (1.44), 2.410 (1.90), m/z = 531 2.429(1.44), 2.523 (3.83), 2.670 (0.81), [M + H]+ 2.710 (1.10), 2.849 (1.01),2.868 (1.33), 2.889 (1.90), 2.976 (0.95), 2.987 (1.07), 2.999 (1.01),3.008 (0.98), 3.563 (4.90), 4.171 (1.21), 4.188 (1.44), 4.194 (3.17),4.212 (3.11), 4.218 (3.26), 4.236 (3.11), 4.241 (1.53), 4.260 (1.15),5.535 (2.02), 5.554 (1.96), 7.214 (2.13), 7226 (2.80), 7.230 (3.14),7.243 (2.57), 7.247 (2.80), 7.261 (1.53), 7.265 (1.27), 7.275 (3.06),7.292 (1.38), 7.408 (2.42), 7.425 (1.96), 7.652 (1.99), 7.657 (4.73),7.662 (5.19), 7.673 (16.00), 7.678 (9.23), 7.714 (2.36), 7.732 (3.11),7.735 (2.85), 7.753 (2.88), 7.882 (3.20), 7.885 (3.57), 7.900 (2.74),7.903 (2.68), 8.304 (3.11), 8.308 (3.23), 8.325 (2.91), 8.329 (2.77),8.812 (11.70), 9.046 (2.62), 9.066 (2.51). 349 LC-MS ¹H-NMR (500 MHz,DMSO-d6) δ [ppm]: (METHOD 0.997 (1.88), 1.009 (1.89), 1.256 (13.03),L5): Rt = 1.268 (13.05), 1.324 (13.05), 1.337 1.37 min; (13.09), 1.963(1.17), 1.978 (1.34), 1.987 MS (1.38), 2.004 (1.32), 2.514 (1.83), 2.523(ESIpos): (1.17), 2.852 (1.36), 2.868 (1.69), 2.884 m/z = 490 (2.08),2.900 (0.98), 2.986 (1.14), 2.995 [M + H]+ (1.24), 3.004 (1.25), 3.012(1.20), 3.018 (0.90), 3.027 (0.85), 4.801 (0.80), 4.813 (2.08), 4.825(2.81), 4.837 (2.05), 4.850 (0.77), 5.526 (0.97), 5.541 (2.48), 5.557(2.44), 5.571 (0.85), 7.222 (2.17), 7.227 (3.29), 7.233 (4.98), 7.241(4.15), 7.245 (3.67), 7.256 (1.43), 7.260 (1.07), 7.274 (3.36), 7.287(1.98), 7.291 (1.44), 7.404 (2.36), 7.408 (2.57), 7.420 (2.24), 7.649(3.36), 7.652 (6.92), 7.656 (4.92), 7.681 (16.00), 7.685 (13.01), 7.704(2.74), 7.718 (3.50), 7.720 (3.56), 7.735 (3.17), 7.878 (3.68), 7.881(4.09), 7.892 (3.13), 7.895 (3.25), 8.306 (3.47), 8.309 (3.76), 8.323(3.28), 8.326 (3.32), 8.861 (12.86), 8.984 (3.14), 9.001 (3.06). 3505.06 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 1.303 (2.43),1.322 (5.61), 1.341 (2.50), L1): Rt = 3.252 (2.09), 3.271 (2.06), 4.250(1.06), 1.35 min; 4.259 (1.62), 4.268 (1.95), 4.275 (1.54), MS 4.284(1.06), 5.305 (0.92), 5.325 (0.92), (ESIpos): 6.783 (1.53), 6.785(1.66), 6.803 (1.75), m/z = 477 6.806 (1.83), 6.911 (0.78), 6.914(0.83), [M + H]+ 6.930 (1.72), 6.932 (1.71), 6.948 (1.03), 6.951 (1.00),7.149 (0.86), 7.153 (0.89), 7.170 (1.43), 7.350 (1.48), 7.370 (1.41),7.652 (16.00), 7.752 (1.09), 7.770 (1.68), 7.791 (1.47), 7.871 (1.93),7.874 (2.04), 7.889 (1.44), 7.892 (1.42), 8.319 (1.50), 8.322 (1.58),8.340 (1.43), 8.343 (1.39), 8.839 (5.77), 9.102 (1.60), 9.123 (1.55).351 5.1 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]: −9.10 (d, 1H),8.81 (s, 1H), 8.30 L1): Rt = (d, 1H), 8.28 (br d, 1H), 7.71-7.84 1.36min; (m, 2H), 7.46 (t, 1H), 7.30-7.40 (m, MS 3H), 7.12-7.22 (m, 1H),6.93 (td, 1H), (ESIpos): 6.79 (dd, 1H), 5.24-5.37 (m, 1H), m/z = 4714.19-4.33 (m, 2H), 3.26 (q, 3H), [M + H]+ 2.64-2.74 (m, 2H), 2.16-2.27(m, 1H), 2.01-2.12 (m, 1H), 1.32 (t, 3H), 1.23 (t, 3H). 352 LC-MS ¹H-NMR(400 MHz, DMSO-d6): δ (Method [ppm] = 9.08 (d, 1H), 8.82 (s, 1H), L1):Rt = 8.25 (dd, 1H), 7.73-7.83 (m, 2H), 7.44 1.26 min; (s, 1H), 7.30-7.38(m, 3H), 7.17 (t, 1H), MS 6.93 (t, 1H), 6.80 (d, 1H), 5.75 (s, 1H),(ESIpos): 528-5.34 (m, 1H), 4.22-4.32 (m, 2H), m/z = 443 2.79 (s, 3H),2.39 (s, 3H), 2.17-2.26 [M + H]+ (m, 1H), 2.03-2.12 (m, 1H). 353 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 0.008 (0.60), 2.086 (0.58),2.094 (0.47), L1): Rt = 2.203 (0.46), 2.214 (0.45), 2.225 (0.41), 1.28min; 2.794 (10.72), 4.248 (0.87), 4.271 (1.29), MS 4.276 (1.30), 4.286(0.77), 5.299 (0.74), (ESIpos): 5.318 (0.76), 5.754 (1.41), 6.787(1.44), m/z = 463 6.808 (1.54), 6.911 (0.70), 6.928 (1.45), [M + H]+6.946 (0.85), 7.150 (0.73), 7.154 (0.77), 7.171 (1.18), 7.189 (0.58),7.353 (1.24), 7.372 (1.13), 7.656 (16.00), 7.754 (1.00), 7.772 (1.46),7.793 (1.32), 7.884 (1.64), 7.886 (1.70), 7.901 (1.28), 7.904 (1.19),8.285 (1.42), 8.288 (1.42), 8.306 (1.32), 8.309 (1.24), 8.844 (4.54),9.082 (1.27), 9.103 (1.21). 354 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (0.46), 0.008 (0.44), 1.175 (0.60), L6): Rt = 1.187(0.74), 1.193 (1.32), 1.205 (1.44), 2.46 min; 1.211 (0.70), 1.223(0.71), 2.073 (0.67), MS 2.523 (0.41), 3.168 (16.00), 4.201 (0.40),(ESIneg): 4.218 (0.81), 4.227 (0.56), 4.236 (0.80), m/z = 558 4245(0.62), 6.804 (0.95), 6.826 (0.84), [M − H]− 7.683 (3.23), 7.897 (0.42),8.001 (0.60), 8.018 (0.44), 9.111 (0.89), 9.124 (0.80). 355 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (3.59), 0.008 (2.29), 2.135(0.68), L1): Rt = 2.224 (0.56), 2.327 (1.51), 2.366 (1.57), 1.25 min;2.522 (5.91), 2.669 (1.22), 2.710 (0.80), MS 4.264 (1.54), 4.275 (1.87),4.710 (5.79), (ESIpos): 5.292 (0.89), 5.311 (0.86), 6.798 (1.54), m/z =488 6.816 (1.69), 6.896 (0.83), 6.915 (1.63), [M + H]+ 6.933 (0.95),7.163 (0.83), 7.180 (1.34), 7.198 (0.65), 7.384 (1.40), 7.404 (1.25),7.678 (16.00), 7.883 (1.10), 7.901 (1.66), 7.923 (1.51), 7.989 (2.02),8.004 (1.40), 8.417 (1.57), 8.435 (1.45), 9.029 (5.19), 9.375 (1.45),9.395 (1.34). 356 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] =9.12 (d, 1H), 8.83 (s, 1H), 8.33 L1): Rt = (d, 1H), 7.88 (d, 1H),7.72-7.79 (m, 1.41 min; 1H), 7.65 (s, 3H), 7.36 (d, 1H), 7.14- MS 7.22(m, 1H), 6.93 (t, 1H), 6.80 (d, 1H), (ESIpos): 5.25-5.37 (m, 1H),4.20-4.34 (m, m/z = 491 2H), 3.17-3.26 (m, 2H), 2.20 (td, 1H), [M + H]+1.99-2.11 (m, 1H), 1.64-1.78 (m, 2H), 1.02 (t, 3H). 357 LC-MS ¹H-NMR(400 MHz, DMSO-d6): δ (Method [ppm] = 8.89-9.00 (m, 2H), 8.04 (d, L1):Rt = 1H), 7.90 (d, 1H), 7.72-7.80 (m, 1H), 1.39 min; 7.67 (s, 3H),7.28-7.39 (m, 1H), 7.16 MS (t, 1H), 6.92 (t, 1H), 6.78 (d, 1H), 5.54(ESIpos): (s, 1H), 5.19-5.29 (m, 1H), 5.03 (br s, m/z = 489 1H),4.17-4.33 (m, 2H), 2.11-2.28 [M + H]+ (m, 4H), 2.02 (br s, 1H). 358 4.9LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 0.640 (1.22), 0.650(1.42), 0.658 (1.28), L1): Rt = 0.668 (0.69), 0.681 (0.74), 0.691(1.29), 1.34 min; 0.698 (1.52), 0.709 (1.18), 1.173 (1.12), MS 1.186(2.68), 1.200 (2.43), 1203 (2.55), (ESIpos): 1.216 (0.95), 2.067 (0.40),2.073 (0.54), m/z = 489 2.079 (0.80), 2.085 (0.85), 2.095 (0.95), [M +H]+ 2.107 (1.22), 2.112 (1.05), 2.118 (0.74), 2.124 (0.52), 2.201(0.53), 2.208 (0.81), 2.218 (1.13), 2.228 (1.10), 2.235 (1.08), 2.246(0.78), 2.253 (0.54), 2.409 (0.51), 2.420 (1.04), 2.426 (1.14), 2.437(1.81), 2.449 (1.05), 2.455 (1.00), 2.466 (0.59), 4.230 (0.57), 4.235(0.67), 4.252 (1.84), 4.258 (1.37), 4.269 (1.59), 4.275 (1.46), 4.280(1.41), 4.287 (1.66), 4.293 (1.43), 4.300 (1.50), 4.310 (0.60), 4.315(0.65), 4.322 (0.46), 5.280 (0.80), 5.291 (1.74), 5.307 (1.69), 5.318(0.75), 6.783 (3.28), 6.799 (3.54), 6.905 (1.59), 6.920 (3.31), 6.934(1.85), 7.148 (1.91), 7.165 (2.68), 7.179 (1.30), 7.367 (2.83), 7.382(2.86), 7.648 (16.00), 7.770 (1.92), 7.784 (3.02), 7.801 (2.71), 7.869(3.37), 7.871 (3.35), 7.884 (2.52), 8.601 (2.89), 8.618 (2.72), 8.787(0.65), 8.816 (9.10), 9.011 (2.78), 9.027 (2.65). 359 LC-MS ¹H-NMR (500MHz, DMSO-d6) δ [ppm]: (Method −0.007 (1.53), 0.006 (1.15), 1.527(11.61), L1): Rt = 1.542 (11.90), 1.554 (11.58), 1.568 1.38 min;(11.39), 2.024 (0.41), 2.037 (0.85), 2.044 MS (0.90), 2.052 (0.94),2.057 (0.92), 2.065 (ESIpos): (1.24), 2.071 (1.06), 2.078 (0.75), 2.084m/z = 491 (0.55), 2.177 (0.52), 2.184 (0.80), 2.194 [M + H]+ (1.16),2.204 (1.11), 2.211 (1.11), 2.221 (0.74), 2.518 (0.93), 2.522 (0.72),3.841 (0.48), 3.855 (1.08), 3.869 (1.42), 3.883 (1.05), 3.898 (0.42),4218 (0.51), 4.224 (0.67), 4.240 (2.00), 4.247 (1.53), 4257 (2.08),4.262 (2.36), 4.268 (1.99), 4.274 (1.55), 4.281 (1.68), 4.290 (0.52),4.297 (0.62), 4.303 (0.43), 5.264 (0.80), 5.276 (1.75), 5.292 (1.70),5.303 (0.77), 6.784 (3.41), 6.798 (3.68), 6.916 (1.72), 6.918 (1.66),6.930 (3.46), 6.945 (2.02), 7.151 (1.65), 7.154 (1.69), 7.168 (2.77),7.182 (1.36), 7.185 (1.32), 7.353 (2.85), 7.368 (2.66), 7.616 (12.83),7.620 (16.00), 7.643 (4.67), 7.647 (6.31), 7.651 (2.84), 7.720 (2.36),7.735 (3.26), 7.738 (2.76), 7.752 (2.91), 7.840 (3.95), 7.842 (3.96),7.854 (3.15), 7.856 (2.93), 8.446 (3.04), 8.461 (2.92), 8.757 (12.10),9.108 (3.03), 9.125 (2.93). 360 LC-MS ¹H-NMR (600 MHz, DMSO-d6) δ [ppm]:(Method 0.005 (1.55), 2.061 (0.52), 2.067 (0.77), L1): Rt = 2.071(0.86), 2.079 (0.95), 2.083 (0.89), 1.12 min; 2.090 (1.10), 2.094(0.95), 2.101 (0.63), MS 2.197 (0.52), 2.202 (0.70), 2.211 (1.08),(ESIpos): 2.219 (1.07), 2.225 (1.08), 2.234 (0.81), m/z = 506 2.386(0.48), 2.517 (1.21), 2.520 (1.17), [M + H]+ 2.523 (0.96), 2.614 (0.48),4.190 (1.43), 4.199 (0.87), 4.204 (1.08), 4215 (5.45), 4.223 (1.99),4.229 (4.83), 4.253 (1.43), 4.266 (1.08), 4.271 (1.32), 4.277 (1.21),4.283 (1.51), 4.290 (0.72), 4.296 (0.76), 4.301 (0.61), 5278 (0.77),5.288 (1.58), 5.301 (1.57), 5.310 (0.71), 6.785 (3.04), 6.798 (3.20),6.888 (1.54), 6.890 (1.54), 6.901 (3.04), 6.913 (1.75), 6.915 (1.67),7.152 (1.45), 7.154 (1.49), 7.166 (2.44), 7.177 (1.22), 7.180 (1.20),7.355 (2.91), 7.366 (4.77), 7.659 (8.30), 7.661 (16.00), 7.667 (5.88),7.670 (4.36), 7.673 (1.81), 7.773 (2.24), 7.785 (2.96), 7.787 (2.70),7.799 (2.65), 7.898 (3.37), 7.899 (3.46), 7.909 (2.76), 7.911 (2.71),8.004 (2.52), 8.349 (2.84), 8.350 (2.88), 8.363 (2.68), 8.365 (2.58),8.951 (10.28), 9.490 (2.95), 9.504 (2.84). 361 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.008 (0.70), 0.008 (0.49), 1.398 L1): Rt =(16.00), 1.988 (0.45), 2.519 (0.43), 6.790 1.44 min; (0.48), 6.849(0.44), 6.851 (0.45), 6.870 MS (0.51), 6.872 (0.48), 6.966 (0.40), 7.673(ESIpos): (0.41), 7.696 (4.12), 7.933 (0.43), 7.951 m/z = 474 (0.60),7.953 (0.54), 7.972 (0.53), 8.054 [M + H]+ (0.67), 8.057 (0.62), 8.071(0.49), 8.075 (0.41), 9.279 (0.96), 9.311 (0.50). 362 LC-MS ¹H-NMR (400MHz, DMSO-d6) delta (Method [ppm]: −0.008 (3.35), 0.008 (3.09), L1): Rt= 1.942 (0.95), 1.962 (1.01), 1.973 (1.12), 1.25 min; 1.994 (1.07),2.877 (0.97), 2.897 (1.34), MS 3.072 (2.46), 3.089 (5.60), 3.105 (2.97),(ESIpos): 3.287 (1.80), 3.448 (1.02), 3.452 (1.05), m/z = 509 3.463(2.26), 3.469 (2.04), 3.479 (2.06), [M + H]+ 3.483 (2.02), 3.500 (0.82),4.961 (1.79), 4.975 (4.01), 4.989 (1.75), 5.573 (1.56), 5.593 (1.55),5.754 (4.61), 7.226 (2.94), 7.234 (3.06), 7.240 (3.44), 7.248 (5.14),7.258 (1.67), 7.266 (2.16), 7.276 (1.40), 7.279 (1.19), 7.511 (1.39),7.523 (1.39), 7.533 (1.20), 7.657 (3.86), 7.659 (5.48), 7.663 (16.00),7.667 (6.58), 7.670 (3.35), 7.673 (2.04), 7.676 (1.25), 7.683 (0.83),7.839 (1.73), 7.857 (2.68), 7.860 (1.98), 7.879 (2.73), 7.927 (2.89),7.931 (3.10), 7.945 (2.00), 7.949 (1.80), 8.630 (2.51), 8.634 (2.52),8.651 (2.41), 8.655 (2.15), 8.879 (10.16), 9.027 (2.07), 9.048 (2.05).363 LC-MS ¹H-NMR (400 MHz, DMSO-d6) delta (Method [ppm]: −0.008 (2.58),0.008 (2.57), L1): Rt = 1.356 (1.00), 2.085 (16.00), 4.144 (1.13), 1.37min; 5.754 (1.90), 6.743 (1.76), 6.747 (2.04), MS 6.764 (1.98), 6.767(2.24), 6.788 (1.04), (ESIpos): 6.791 (1.01), 6.807 (2.03), 6.810(1.93), m/z = 558 6.826 (1.26), 6.829 (1.15), 6.992 (1.32), [M + H]+6.995 (2.52), 6.997 (1.59), 7.013 (1.50), 7.015 (2.62), 7.017 (1.66),7.111 (0.95), 7.116 (1.01), 7.132 (1.62), 7.138 (1.65), 7.141 (1.44),7.150 (2.04), 7.153 (2.12), 7.157 (1.66), 7.159 (1.41), 7.169 (1.40),7.171 (1.37), 7.265 (1.54), 7.285 (1.54), 7.584 (1.21), 7.589 (1.25),7.604 (1.61), 7.609 (1.64), 7.623 (1.04), 7.628 (1.04), 7.681 (0.99),7.684 (1.64), 7.686 (2.60), 7.690 (5.09), 7.695 (12.74), 7.698 (4.45),7.700 (3.56), 7.734 (1.72), 7.751 (2.14), 7.755 (2.02), 7.773 (2.10),7.916 (2.37), 7.919 (2.53), 7.934 (2.01), 7.938 (1.93), 8.298 (1.27),8.300 (1.54), 8.303 (1.59), 8.305 (1.45), 8.310 (1.37), 8.312 (1.59),8.315 (1.49), 8.317 (1.32), 8.336 (2.29), 8.339 (2.36), 8.357 (2.07),8.361 (1.99), 9.071 (8.31), 9.124 (1.92), 9.144 (1.88). 364 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.66), 0.008 (2.57), 2.119(1.04), L1): Rt = 2.128 (0.86), 2.366 (0.82), 2.710 (0.82), 1.28 min;3.060 (2.72), 3.077 (6.64), 3.093 (3.50), MS 3.287 (2.70), 3.438 (1.04),3.454 (2.48), (ESIpos): 3.468 (3.16), 3.481 (2.10), 3.497 (0.89), m/z =525 4.254 (1.46), 4.263 (1.26), 4.273 (2.24), [M + H]+ 4.282 (2.43),4.297 (1.35), 4.946 (2.06), 4.960 (4.56), 4.974 (1.99), 5.291 (1.28),5.310 (1.31), 6.781 (2.41), 6.784 (2.61), 6.802 (2.74), 6.805 (2.88),6.910 (1.33), 6.913 (1.46), 6.928 (2.63), 6.932 (2.57), 6.947 (1.59),6.950 (1.53), 7.151 (1.31), 7.156 (1.35), 7.173 (2.21), 7.190 (1.24),7.194 (1.13), 7.448 (2.17), 7.465 (2.06), 7.627 (1.00), 7.632 (1.04),7.658 (5.73), 7.662 (16.00), 7.666 (6.68), 7.669 (3.41), 7.675 (1.22),7.838 (1.93), 7.856 (2.97), 7.859 (2.35), 7.877 (2.92), 7.929 (3.21),7.932 (3.50), 7.946 (2.21), 7.950 (2.06), 8.624 (2.97), 8.627 (2.97),8.645 (2.70), 8.649 (2.50), 8.881 (10.45), 9.155 (2.48), 9.175 (2.37).365 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.150 (1.77),−0.008 (16.00), 0.008 L1): Rt = (14.17), 0.146 (1.65), 1.236 (0.71),2.104 1.32 min; (1.48), 2.217 (1.18), 2.327 (3.48), 2.366 MS (2.13),2.523 (12.52), 2.669 (3.84), 2.709 (ESIpos): (2.18), 4.249 (2.01), 4.269(2.72), 4.297 m/z = 507 (1.83), 5.284 (1.83), 5.303 (1.89), 5.754 [M +H]+ (4.66), 6.784 (3.66), 6.804 (4.13), 6.917 (1.89), 6.932 (3.60),6.951 (2.36), 7.155 (1.89), 7.173 (2.89), 7.193 (1.54), 7.357 (3.25),7.362 (7.38), 7.366 (5.20), 7.394 (13.99), 7.398 (11.04), 7.430 (3.01),7.447 (2.95), 7.814 (2.48), 7.832 (4.07), 7.853 (4.07), 7.892 (4.43),7.896 (4.84), 7.910 (2.89), 8.550 (3.96), 8.554 (3.84), 8.571 (3.72),8.575 (3.48), 8.841 (14.23), 9.114 (3.31), 9.135 (3.25). 366 4.79 ¹H-NMR(399, 9532 MHz, DMSO): δ = 9.129 (0.47); 9.1148 (0.47); 9.1094 (0.47);8.7855 (1.25); 8.7775 (1.27); 8.6377 (0.78); 8.6169 (0.83); 7.8685(0.52); 7.8505 (0.85); 7.8295 (0.79); 7.7781 (1.03); 7.7634 (0.65);7.7608 (0.66); 7.7301 (0.69); 7.7265 (0.81); 7.7101 (0.84); 7.7068(0.92); 7.4773 (0.34); 7.4638 (0.65); 7.4576 (0.71); 7.4446 (0.66);7.4301 (0.75); 7.4129 (0.41); 7.3928 (0.56); 7.3822 (0.55); 7.3662(0.35); 7.1798 (0.35); 7.1614 (0.7); 7.1419 (0.43); 6.9335 (0.47); 6.915(0.8); 6.8966 (0.39); 6.7926 (0.94); 6.7722 (0.84); 5.2907 (0.43);5.2723 (0.45); 4.2863 (0.4); 4.2718 (0.77); 4.263 (0.76); 4.2526 (0.49);4.2448 (0.48); 3.3189 (19.02); 3.0568 (0.38); 3.0385 (1.18); 3.0201(1.27); 3.0017 (0.5); 2.5053 (32.31); 2.501 (45.79); 2.4969 (38.72);1.3977 (16); 1.1703 (1.73); 1.1519 (3.55); 1.1335 (1.74); 0.0074 (1.2);−0.0002 (26.74) 367 5.48 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.1306(2.01); 9.1101 (2.05); 8.8861 (7.98); 8.6364 (2); 8.6333 (2.17); 8.6154(2.23); 8.6122 (2.26); 7.9429 (1.75); 7.9397 (1.94); 7.925 (2.69);7.9218 (2.64); 7.8638 (2.19); 7.8429 (2.42); 7.8248 (1.46); 7.6937(0.7); 7.6622 (16); 7.458 (1.87); 7.4401 (1.96); 7.1926 (0.85); 7.1892(0.9); 7.1715 (1.84); 7.1543 (1.13); 7.1505 (1.13); 6.948 (1.34); 6.9295(2.26); 6.9106 (1.06); 6.8025 (2.51); 6.7834 (2.23); 6.5799 (0.36);5.7548 (2.41); 5.3226 (0.52); 5.3079 (1.15); 5.2891 (1.14); 5.2746(0.5); 4.3171 (0.37); 4.2984 (1.12); 4.2828 (2.04); 4.2742 (1.92);4.2638 (1.11); 4.2555 (1.22); 4.2357 (0.36); 3.3221 (28.56); 3.0452(1.38); 3.0269 (4.39); 3.0085 (4.61); 2.9901 (1.55); 2.9503 (2.63);2.5062 (35.71); 2.5018 (49.01); 2.4975 (37.88); 2.2455 (0.37); 2.2396(0.4); 2.2253 (0.63); 2.2154 (0.69); 2.2039 (0.74); 2.1923 (0.58); 2.183(0.34); 2.1277 (0.35); 2.1193 (0.52); 2.1122 (0.71); 2.1045 (0.86);2.0944 (0.61); 2.0876 (0.59); 2.078 (0.53); 2.0688 (0.48); 1.397 (6.52);1.2337 (0.54); 1.1701 (1.44); 1.1529 (5.39); 1.1345 (11.03); 1.1161(5.17); 0.0078 (2.03); −0.0002 (46.62) 368 3.76 ¹H-NMR (399, 9532 MHz,DMSO): δ = 9.4079 (0.91); 9.3936 (0.81); 9.3876 (0.93); 9.348 (0.54);9.3284 (1.17); 9.3084 (0.7); 9.2139 (0.51); 9.2004 (1.18); 9.1877(1.26); 9.1743 (0.63); 9.1376 (0.37); 9.124 (0.46); 9.1127 (0.45);9.0815 (0.48); 9.069 (0.72); 9.0563 (0.54); 8.9299 (4.95); 8.9181(2.18); 8.3146 (0.48); 7.8564 (6.67); 7.8446 (5.81); 7.8246 (0.32);7.7421 (2.74); 7.7383 (2.93); 7.7222 (3.38); 7.7184 (3.39); 7.4976(0.59); 7.4918 (1.24); 7.4783 (1.38); 7.4723 (2.72); 7.4633 (1.1);7.4588 (1.07); 7.4523 (1.75); 7.4438 (0.68); 7.429 (1.04); 7.4219(1.82); 7.4179 (1.54); 7.4031 (1.84); 7.399 (1.97); 7.3891 (1.42);7.3854 (1.42); 7.38 (0.92); 7.3699 (1.26); 7.3497 (0.86); 7.3415 (0.86);7.1887 (1.08); 7.1706 (2.27); 7.1526 (1.33); 6.9372 (1.41); 6.9184(2.37); 6.8998 (1.11); 6.8025 (2.56); 6.782 (2.28); 5.7548 (16); 5.244(0.78); 5.2248 (1.32); 4.3011 (0.47); 4.2715 (1.25); 4.2597 (1.64);4.2386 (1.15); 4.2313 (1.34); 4.2105 (1.16); 4.19 (0.42); 4.0556 (0.74);4.0378 (2.3); 4.02 (2.33); 4.0022 (0.78); 3.6324 (0.57); 3.6282 (0.47);3.6193 (0.65); 3.6135 (1.07); 3.6005 (1.04); 3.595 (0.97); 3.5876(0.71); 3.5816 (1.03); 3.569 (0.62); 3.5629 (0.59); 3.4779 (0.67);3.3947 (0.75); 3.3771 (0.89); 3.3607 (0.77); 3.3457 (1.02); 3.3189(76.03); 3.3011 (0.56); 3.2956 (0.52); 3.2762 (0.74); 2.6748 (0.91);2.6703 (1.21); 2.6656 (0.94); 2.5235 (3.02); 2.5099 (69.23); 2.5056(147.9); 2.501 (208.96); 2.4966 (158.74); 2.4924 (78.18); 2.3323 (0.85);2.328 (1.2); 2.3235 (0.9); 2.2195 (0.41); 2.2066 (0.59); 2.1969 (0.68);2.1869 (0.78); 2.1765 (0.84); 2.1662 (0.77); 2.1545 (0.61); 2.0945(0.63); 2.085 (0.73); 2.0685 (0.72); 2.0511 (0.6); 1.9884 (9.96); 1.3946(1.94); 1.3881 (1.89); 1.376 (4.14); 1.3695 (3.96); 1.3626 (3.1); 1.3577(2.54); 1.3506 (2.19); 1.344 (5.38); 1.3253 (2.43); 1.1927 (2.64);1.1749 (5.28); 1.1571 (2.56); 0.008 (1.98); −0.0001 (61.25); −0.0084(2.3) 369 3.94 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.2003 (2.67); 9.1806(3.23); 9.167 (2.01); 9.0322 (8.51); 9.019 (6.5); 8.9438 (4.48); 8.9221(4.91); 8.3143 (2.06); 7.9838 (3.69); 7.9659 (6.23); 7.9442 (6.22);7.9065 (7.21); 7.889 (4.28); 7.7531 (5.21); 7.7495 (5.57); 7.7332(6.28); 7.7295 (6.44); 7.508 (2.22); 7.4958 (2.14); 7.4886 (4.93);7.4766 (4.41); 7.4689 (3.41); 7.4566 (5.08); 7.432 (6.44); 7.4078(3.86); 7.3882 (1.78); 7.1782 (1.86); 7.1588 (3.64); 7.1396 (2.31);6.9267 (1.91); 6.9158 (2); 6.908 (3.3); 6.8978 (2.95); 6.8915 (1.75);6.8809 (1.36); 6.789 (5.67); 6.7684 (5.12); 5.7544 (10.27); 5.214(1.39); 5.2001 (2.98); 5.1805 (2.91); 5.1675 (1.28); 4.305 (1.02);4.2955 (1.49); 4.2776 (2.26); 4.2627 (2.39); 4.2546 (1.65); 4.2028(1.82); 4.1938 (1.6); 4.1816 (2.42); 4.1738 (2.22); 4.1539 (1.1), 4.0375(0.53); 4.0197 (0.62); 3.9026 (0.65); 3.7185 (0.69); 3.7005 (2.39);3.6828 (6.64); 3.6642 (7.29); 3.6477 (3.14); 3.631 (1.2); 3.6135 (0.55);3.5953 (0.33); 3.3784 (0.72); 3.3184 (262.18); 2.675 (3.55); 2.6703(4.96); 2.666 (3.64); 2.5236 (12.22); 2.5055 (584.02); 2.5011 (819.49);2.4967 (626.86); 2.3325 (3.45); 2.3279 (4.64); 2.3235 (3.47); 2.1791(1.23); 2.1677 (1.59); 2.1578 (1.93); 2.1464 (2.45); 2.133 (2.65);2.1234 (2.57); 2.0956 (1.25); 2.0828 (0.81); 1.9882 (2.46); 1.3887(0.5); 1.3197 (7.73); 1.3046 (14.27); 1.301 (16); 1.2858 (7.08); 1.2826(7.64); 1.2589 (1.64); 1.2352 (4.77); 1.193 (1.14); 1.1751 (1.98);1.1573 (1.17); 1.1406 (0.7); 1.1176 (0.38); 1.0977 (0.35); 0.8541(0.85); 0.8372 (0.72); 0.768 (0.51); 0.7585 (0.6); 0.7287 (0.37); 0.1458(0.91); 0.0079 (6.73); −0.0002 (210.64); −0.0083 (8.7); −0.1499 (0.88)370 4.44 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.3994 (1.2), 9.3782 (2.63),9.3572 (1.64), 9.1706 (1.25), 9.1482 (2.41), 9.1234 (1.62), 9.0407(6.79), 9.0256 (5.14), 8.0137 (2.95), 7.9958 (3.69), 7.8636 (2.22),7.8447 (3.05), 7.824 (1.78), 7.6865 (2.25), 7.6816 (5.53), 7.6774(5.78), 7.6659 (16), 7.6613 (10.26), 7.4424 (1.15), 7.4242 (1.23),7.3796 (1.54), 7.3615 (1.65), 7.1997 (1.27), 7.1795 (2.54), 7.1609(1.67), 6.9491 (1.99), 6.9307 (3.38), 6.9119 (1.61), 6.8111 (3.75),6.7907 (3.34), 5.7549 (6.05), 5.2713 (0.45), 5.2578 (1.23), 5.239(1.43), 5.2251 (1.09), 5.2116 (0.34), 4.3107 (0.44), 4.3029 (0.54),4.2848 (1.37), 4.2718 (2.3), 4.2635 (1.9), 4.2523 (1.39), 4.2444 (1.58),4.2328 (0.73), 4.2244 (1.04), 4.217 (0.53), 4.2041 (0.33), 3.6141(0.78), 3.6102 (0.99), 3.5958 (1.19), 3.5918 (1.15), 3.5813 (1.08),3.5775 (1.52), 3.5627 (1.01), 3.5591 (1.28), 3.5409 (0.4), 3.3918 (1.1),3.3729 (1.38), 3.3592 (1.03), 3.353 (1.23), 3.3401 (1.19), 3.3338 (1.2),3.3202 (28.4), 3.3014 (0.76), 2.675 (0.44), 2.6707 (0.61), 2.6662(0.47), 2.5235 (1.63), 2.5058 (73.82), 2.5014 (103.74), 2.497 (80.59),2.493 (41.24), 2.3326 (0.43), 2.3281 (0.59), 2.3239 (0.48), 2.2328(0.49), 2.2203 (0.71), 2.2113 (0.74), 2.1984 (1.03), 2.1872 (0.95),2.1772 (0.91), 2.165 (0.61), 2.155 (0.35), 2.1416 (0.36), 2.1271 (0.7),2.1187 (0.84), 2.1036 (0.67), 2.0935 (0.67), 2.0842 (0.76), 2.0783(0.75), 2.0684 (0.55), 2.0605 (0.45), 2.0507 (0.37), 2.0437 (0.32),1.3819 (3.75), 1.3633 (8.24), 1.3575 (3.82), 1.3445 (4.22), 1.3387(6.43), 1.3199 (2.77), 1.2332 (0.72), 1.1754 (0.4), −0.0002 (0.66) 3714.54 ¹H-NMR (399, 9532 MHz, DMSO): δ = 9.1895 (3.04); 9.1694 (3.1);9.1296 (0.37); 9.1153 (10.56); 8.9396 (3.14); 8.9368 (3.35); 8.9178(3.51); 8.915 (3.51); 8.3143 (0.49); 8.0499 (2.68); 8.0473 (2.89);8.0321 (4.35); 8.0293 (4.1); 7.9727 (3.41); 7 .9543 (2.73); 7.951(3.52); 7.9328 (2.34); 7.7006 (3.22); 7.6959 (6.75); 7.6912 (4.54);7.655 (16); 7.6503 (13.06); 7.4831 (2.66); 7.4649 (2.85); 7.1902 (1.31);7.1863 (1.38); 7.1687 (2.79); 7.1515 (1.77); 7.1478 (1.69); 6.9385(2.04); 6.9201 (3.47); 6.9036 (1.63); 6.9012 (1.66); 6.7982 (3.87);6.779 (3.55); 5.7544 (1.92); 5.2344 (0.76); 5.2216 (1.73); 5.2018(1.72); 5.1876 (0.75); 4.3164 (0.62); 4.3031 (0.84); 4.2899 (1.38);4.2793 (1.29); 4.2738 (1.51); 4.2653 (1.02); 4.2225 (0.99); 4.2147(1.33); 4.2016 (1.16); 4.1939 (1.75); 4.1864 (0.87); 4.1743 (0.72);4.1658 (0.65); 3.7057 (0.34); 3.6883 (1.22); 3.6828 (1.08); 3.6702(3.31); 3.6645 (3.08); 3.6516 (3.37); 3.6461 (3.16); 3.6329 (1.16);3.6285 (1.24); 3.3193 (68.59); 2.675 (0.88); 2.6705 (1.18); 2.6659(0.87); 2.5236 (3.14); 2.5101 (69.48); 2.5058 (144.19); 2.5013 (199.43);2.4969 (149.23); 2.4928 (72.67); 2.3326 (0.83); 2.3282 (1.16); 2.3238(0.81); 2.2169 (0.37); 2.204 (0.5); 2.1912 (0.95); 2.1785 (1.25); 2.1702(1.47); 2.1564 (1.69); 2.1486 (1.83); 2.14 (1.59); 2.126 (0.94); 2.1147(0.54); 2.1053 (0.46); 1.3515 (0.39); 1.3055 (7.28); 1.2869 (15.83);1.2685 (7.21); 1.2352 (4.31); 1.17 (0.64); 1.1521 (0.57); 0.8536 (0.58);0.835 (0.32); −0.0002 (1.18) 372 4.08 ¹H-NMR (399, 9532 MHz, DMSO): δ =12.3602 (1.81), 9.1502 (2.55), 9.1301 (2.52), 8.892 (9.63), 8.8835(0.49), 8.6271 (2.4), 8.624 (2.53), 8.6058 (2.71), 8.6028 (2.68), 7.9529(2.14), 7.9502 (2.26), 7.9352 (3.25), 7.9323 (3.12), 7.9076 (0.43),7.8737 (2.65), 7.8528 (2.81), 7.8346 (1.74), 7.6694 (8.23), 7.6663 (16),7.4556 (2.26), 7.4372 (2.36), 7.1902 (1.1), 7.1719 (2.32), 7.1546 (1.4),7.151 (1.4), 6.9475 (1.65), 6.9287 (2.79), 6.91 (1.31), 6.8025 (3.17),6.7815 (2.81), 5.3004 (0.68), 5.2866 (1.49), 5.2669 (1.46), 5.2527(0.64), 4.3167 (0.34), 4.3082 (0.53), 4.2896 (1.41), 4.2737 (2.43),4.2645 (2.36), 4.2534 (1.28), 4.245 (1.54), 4.2252 (0.51), 4.2177 (0.4),4.0377 (0.33), 4.0198 (0.37), 3.3181 (128.86), 3.1629 (2.73), 3.145(6.07), 3.1272 (3.01), 2.89 (0.57), 2.7306 (0.51), 2.6743 (2.28), 2.6697(3.09), 2.6658 (2.38), 2.615 (0.4), 2.597 (0.4), 2.5228 (8.93), 2.5052(404. 28), 2.5009 (529.51), 2.4965 (389.18), 2.477 (6.31), 2.332 (2.29),2.3276 (3.04), 2.323 (2.27), 2.2559 (0.33), 2.2437 (0.53), 2.2366(0.54), 2.2221 (0.88), 2.2127 (1.01), 2.2005 (0.98), 2.1892 (0.78),2.1288 (0.69), 2.1204 (0.93), 2.1136 (1.11), 2.1049 (0.78), 2.0969(0.76), 2.0877 (0.7), 2.0787 (0.66), 1.9883 (1.45), 1.2344 (0.51),1.1925 (0.48), 1.1741 (0.82), 1.1569 (0.42), 1.1054 (0.4), 0.0077(1.78), −0.0003 (53.99), −0.008 (2.53) 373 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 4.172 (16.00 4.245 (0.90), 4.254 (1.07), L1):Rt = 4.269 (1.49), 4.273 (1.51), 4.283 (0.86), 1.39 min; 5.274 (0.83),5.293 (0.83), 5.754 (12.35), MS 6.793 (1.40), 6.796 (1.53), 6.814(1.59), (ESIpos): 6.816 (1.66), 6.909 (0.74), 6.912 (0.74), m/z = 4796.928 (1.55), 6.930 (1.54), 6.946 (0.93), [M + H]+ 6.949 (0.91), 7.159(0.76), 7.163 (0.82), 7.180 (1.29), 7.363 (1.33), 7.380 (1.25), 7.650(0.88), 7.655 (2.07), 7.659 (2.33), 7.670 (7.40), 7.675 (4.39), 7.702(1.20), 7.720 (1.66), 7.723 (1.57), 7.741 (1.47), 7.886 (1.69), 7.890(1.80), 7.904 (1.44), 7.908 (1.42), 8.296 (1.61), 8.299 (1.63), 8.317(1.54), 8.320 (1.45), 8.811 (5.57), 9.192 (1.36), 9.212 (1.34). 1.66384: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.9731 (0.6); 8.9623 (0.6); 8.9531(0.6); 8.9419 (0.5); 8.4859 (0.4); 8.3740 (0.7); 8.3670 (0.7); 8.3565(0.8); 8.3495 (0.8); 8.3209 (2.7); 7.7618 (0.4); 7.7477 (0.4); 7.7333(0.5); 7.7203 (0.4); 7.6684 (1.2); 7.6517 (1.2); 7.6483 (1.4); 7.5524(0.5); 7.5423 (3.3); 7.5361 (1.8); 7.5245 (1.4); 7.5070 (0.4); 7.4333(0.4); 7.4228 (0.5); 7.4138 (0.9); 7.4033 (0.8); 7.3941 (0.6); 7.3837(0.5); 7.3046 (1.3); 7.2862 (1.8); 7.2711 (0.5); 7.1678 (0.5); 7.1476(1.1); 7.1280 (0.6); 6.9086 (0.8); 6.8899 (1.2); 6.8713 (0.6); 6.7857(1.6); 6.7654 (1.3); 5.2479 (0.3); 5.2338 (0.7); 5.2140 (0.7); 4.2573(1.1); 4.2441 (1.8); 4.2314 (1.1); 3.3217 (36.1); 3.0620 (2.2); 3.0560(2.8); 3.0504 (2.7); 3.0439 (2.5); 3.0278 (0.6); 2.5049 (33.4); 2.5007(44.2); 2.4965 (34.0); 2.1736 (0.3); 2.1521 (0.4); 2.1380 (0.6); 2.1241(0.5); 2.0312 (0.5); 2.0163 (0.6); 2.0038 (0.3); 1.9947 (0.4); 1.9884(0.4); 1.3971 (16.0); −0.0002 (19.8) 385 1.55 385: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 8.9954 (0.7); 8.9747 (0.7); 8.4127 (0.8); 8.3889 (3.2);7.8025 (0.5); 7.7890 (0.5); 7.6892 (0.8); 7.6729 (1.1); 7.5759 (0.9);7.5701 (0.4); 7.5551 (1.2); 7.5367 (0.7); 7.3163 (0.7); 7.2977 (0.8);7.1731 (0.7); 7.1561 (1.1); 7.1385 (0.6); 6.9188 (0.5); 6.9014 (0.9);6.8835 (0.4); 6.7948 (1.0); 6.7745 (1.0); 5.2426 (0.5); 5.2229 (0.5);4.2655 (0.8); 4.2517 (1.4); 4.2391 (0.8); 3.3230 (12.3); 3.0662 (2.8);3.0538 (2.8); 2.5055 (17.4); 2.5013 (22.6); 2.4970 (17.0); 2.1478 (0.4);2.1343 (0.4); 2.0450 (0.3); 2.0307 (0.4); 1.9884 (0.9); 1.3974 (16.0);1.1746 (0.4); 0.0078 (0.5); −0.0002 (12.0) 395 1.93 395: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 8.9826 (3.1), 8.9620 (3.2), 8.4484 (2.1), 8.4334(2.3), 8.4245 (2.4), 8.4103 (12.6), 8.3268 (0.6), 7.9292 (1.8), 7.9165(1.8), 7.6580 (3.8), 7.6532 (7.4), 7.6484 (4.2), 7.5327 (2.4), 7.5095(4.5), 7.4864 (2.4), 7.4628 (11.2), 7.4594 (10.8), 7.3192 (0.3), 7.3065(2.9), 7.2879 (3.1), 7.1773 (1.4), 7.1738 (1.4), 7.1563 (2.9), 7.1388(1.9), 7.1353 (1.8), 6.9190 (2.0), 6.9164 (2.2), 6.9001 (3.6), 6.8979(3.8), 6.8819 (1.8), 6.8792 (1.8), 6.7961 (4.0), 6.7940 (4.1), 6.7757(3.7), 6.7735 (3.6), 5.7559 (16.0), 5.2477 (0.8), 5.2330 (1.9), 5.2134(1.9), 5.1997 (0.9), 4.2618 (3.1), 4.2486 (5.4), 4.2356 (3.4), 4.0379(0.4), 4.0202 (0.4), 3.3218 (86.0), 3.0661 (11.7), 3.0536 (11.8), 2.6749(0.6), 26705 (0.8), 2.6660 (0.6), 2.5238 (2.8), 2.5103 (50.5), 2.5060(102.1), 2.5015 (134.9), 2.4970 (97.8), 2.4927 (47.7), 2.3328 (0.6),2.3282 (0.8), 2.3237 (0.6), 2.1916 (0.4), 2.1780 (0.9), 2.1627 (1.0),2.1574 (0.9), 2.1424 (1.6), 2.1289 (1.5), 2.1149 (0.6), 2.0549 (0.5),2.0425 (1.3), 2.0280 (1.5), 2.0205 (0.8), 2.0150 (0.9), 2.0069 (1.1),1.9887 (2.2), 1.3973 (10.5), 1.3516 (0.5), 1.2587 (0.4), 1.2492 (0.3),1.2333 (0.9), 1.1926 (0.5), 1.1748 (1.0), 1.1570 (0.5), 0.0080 (1.2),−0.0001 (34.0), −0.0084 (1.3) 427 3.81 427: ¹H-NMR (400.0 MHz, d₆-DMSO):δ = 8.8749 (4.5); 8.8543 (4.6); 8.6918 (16.0); 8.2529 (4.8); 8.2338(5.1); 8.2316 (5.1); 7.8425 (4.2); 7.8272 (6.1); 7.7693 (4.8); 7.7486(5.2); 7.7304 (3.1); 7.6505 (0.9); 7.6422 (1.0); 7.6350 (1.2); 7.6273(1.9); 7.6235 (2.0); 7.6142 (1.9); 7.6064 (1.9); 7.6016 (1.9); 7.5948(1.2); 7.5866 (1.0); 7.5788 (0.8); 7.4334 (4.3); 7.4147 (4.7); 7.2421(2.4); 7.2322 (2.4); 7.2202 (2.3); 7.1731 (2.1); 7.1554 (4.4); 7.1378(2.7); 6.9373 (3.2); 6.9188 (5.5); 6.9002 (2.6); 6.7863 (6.0); 6.7657(5.5); 5.2365 (1.2); 5.2204 (2.8); 5.2018 (2.8); 5.1875 (1.3); 4.2935(0.8); 4.2753 (2.7); 4.2587 (4.8); 4.2499 (4.6); 4.2384 (2.6); 4.2310(2.9); 4.2102 (0.9); 4.0554 (0.4); 4.0378 (0.9); 4.0205 (0.9); 3.4979(41.4); 3.4611 (0.3); 3.3196 (127.6); 3.2906 (37.1); 3.2593 (0.4);3.2518 (0.4); 2.6711 (1.5); 2.6075 (0.4); 2.5052 (201.2); 2.5014(249.4); 2.3279 (1.4); 2.1701 (1.6); 2.1600 (1.7); 2.1500 (1.9); 2.1376(1.4); 2.1280 (0.8); 2.0556 (1.8); 2.0483 (2.1); 2.0386 (1.5); 2.0298(1.5); 2.0223 (1.3); 2.0126 (1.2); 1.9885 (3.7); 1.3978 (3.7); 1.2364(0.7); 1.1922 (0.9); 1.1746 (1.9); 1.1566 (1.0); −0.0002 (4.5) 445 2.13445: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.4154 (0.6); 8.4123 (0.6); 7.6823(0.4); 7.6786 (0.4); 7.6571 (0.4); 7.6475 (0.4); 7.6400 (0.9); 6.7637(0.4); 5.7524 (16.0); 4.0645 (0.6); 3.8724 (0.6); 3.3200 (2.8); 2.5052(4.9); 2.5008 (6.3); 2.4963 (4.5); 2.3205 (0.4); 1.9880 (0.7); 1.1752(0.4); −0.0002 (4.8) 452 3.94 452: ¹H-NMR (400.0 MHz, d₆-DMSO): δ =8.7209 (3.6); 8.7000 (4.0); 8.6897 (16.0); 8.2701 (3.6); 8.2667 (4.0);8.2490 (4.3); 8.2456 (4.2); 7.8441 (3.0); 7.8409 (3.3); 7.8265 (5.0);7.823 3 (4.6); 7.7697 (4.4); 7.7515 (3.6); 7.7486 (4.4); 7.7308 (2.8);7.6522 (0.7); 7.6444 (0.8); 7.6369 (0.9); 7.6300 (1.4); 7.6246 (1.4);7.6163 (1.4); 7.6081 (1.3); 7.6034 (1.4); 7.5958 (0.9); 7.5887 (0.8);7.5810 (0.6); 7.4927 (0.3); 7.4814 (2.2); 7.4729 (2.9); 7.4605 (2.8);7.2674 (1.3); 7.2549 (3.5); 7.2449 (6.3); 7.2328 (9.0); 7.2219 (8.0);7.2162 (3.8); 7.2103 (4.7); 7.1981 (0.5); 5.7572 (10.3); 5.5284 (1.0);5.5088 (2.9); 5.4887 (2.9); 5.4687 (1.0); 3.4923 (37.5); 3.3247 (16.2);3.3105 (0.7); 3.2922 (32.1); 2.9922 (0.7); 2.9841 (0.8); 2.9705 (0.9);2.9620 (1.0); 2.9529 (1.6); 2.9448 (1.6); 2.9309 (1.6); 2.9228 (1.4);2.8834 (1.1); 2.8630 (2.4); 2.8426 (1.8); 2.8234 (1.2); 2.8026 (0.7);2.5231 (1.6); 2.5094 (15.9); 2.5051 (32.4); 2.5007 (41 5); 2.4962(30.3); 2.4728 (1.7); 2.4643 (1.4); 2.4530 (0.8); 2.4449 (0.6); 1.9656(0.7); 1.9440 (1.9); 1.9342 (0.8); 1.9232 (1.9); 1.9127 (1.8); 1.9014(0.8) 1.8918 (1.7); 1.8700 (0.6) 481 3.33 481: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 9.8434 (0.4); 9.1777 (1.2); 9.1644 (1.4); 9.1583 (1.5);9.1461 (1.1); 8.9656 (0.6); 8.5679 (0.4); 8.5578 (0.4); 8.3141 (0.4);8.2906 (0.3); 8.2685 (0.4); 8.2490 (2.2); 8.2440 (2.2); 8.2295 (2.4);8.2244 (2.4); 8.0111 (0.7); 7.9895 (0.6); 7.9522 (1.0); 7.6897 (2.8);7.6861 (2.8); 7.6697 (3.4); 7.6661 (3.2); 7.6383 (1.3); 7.6206 (3.6);7.6005 (6.3); 7.5945 (4.4); 7.5819 (1.4); 7.5774 (0.8); 7.5191 (0.4);7.5077 (0.4); 7.4986 (0.4); 7.4872 (0.4); 7. 4510 (1.0); 7.4428 (0.9);7.4319 (1.9); 7.4236 (1.7); 7.4122 (1.2); 7.4041 (1.0); 7.3352 (2.6);7.3166 (3.0); 7.3077 (2.3); 7.2883 (0.9); 7.1880 (1.2); 7.1703 (2.4);7.1527 (1.5); 6.9365 (1.3); 6.9169 (2.1); 6.8982 (1.0); 6.8079 (3.2);6.7875 (2.9); 5.7540 (7.8); 5.2734 (1.3); 4.3307 (0.6); 4.3220 (0. 9);4.3038 (1.1); 4.2925 (1.5); 4.2828 (0.9); 4.2350 (1.1); 4.2103 (1.5);4.1831 (0.6); 4.1709 (0.8); 4.0380 (0.6); 4.0202 (0.6); 3.8597 (5.5);3.8494 (7.9); 3.8384 (5.6); 3.5677 (1.0); 3.3182 (55.23); 3.2947 (0.7);3.2627 (6.5); 2.8904 (6.9); 2.7313 (6.1); 2.6743 (0.9); 2.6700 (1.2);2.6657 (0.9); 2.62 38 (0.6); 2.5054 (151.3); 2.5010 (194.0); 2.4966(144.4); 2.4305 (16.0); 2.3321 (0.9); 2.3276 (1.2); 2.3234 (0.8); 2.2815(0.4); 2.2703 (0.6); 2.2584 (0.6); 2.2457 (1.0); 2.2346 (1.0); 2.2223(0.8); 2.2102 (0.7); 2.0907 (1.1); 2.0764 (0.8); 2.0611 (0.8); 1.9881(2.2); 1.9643 (2.5); 1.9078 (0.7); 1.2982 (0.8); 1.2586 (1.2); 1.2354(1.8); 1.1925 (0.7); 1.1749 (1.3); 1.1570 (0.7); 1.0448 (0 8); 1 0296(0.9); 0.8533 (0.5); 0.8367 (0.4); −0.0002 (20.1) 482 4.36 482: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.2312 (1.6); 9.2113 (1.7); 8.8635 (0.8);8.8560 (0.7); 8.6870 (4.9); 8.6846 (4.8); 8.4211 (0.4); 8.4187 (0.4);8.4001 (0.5); 8.3976 (0.5); 8.3288 (2.1); 8.3253 (2.2); 8.3085 (2.4);8.3046 (2.3); 7.9518 (2.0); 7.9399 (0.4); 7.9219 (0.6); 7.9013 (0.5);7.8692 (0.6); 7.8658 (0.7); 7.8512 (0.4); 7.8481 (0.4); 7.7575 (1.4);7.7398 (3.3); 7.7265 (0.8); 7.7194 (3.5); 7.7134 (3.1); 7.7092 (5.0);7.7044 (3.8); 7.6931 (3.6); 7.6900 (4.4); 7.4756 (0.6); 7.4676 (0.9);7.4573 (1.2); 7.4481 (1.9); 7.4380 (1.7); 7.4285 (1.2); 7.4184 (1.1);7.4106 (0.4); 7.4063 (0.5); 7.3859 (0.6); 7.3624 (3.5); 7.3434 (4.0);7.3282 (1.0); 7.1883 (1.2); 7.1679 (2.6); 7.1496 (1.6); 6.9420 (0.4);6.9215 (1.7); 6.9027 (2.5); 6.8841 (1.1); 6.8042 (3.6); 6.7838 (3.2);6.4934 (0.6); 6.3542 (1.2); 6.2153 (0.6); 5.2813 (0.6); 5.2666 (1.4);5.2495 (1.3); 5.2341 (0.6); 4.3072 (0.4); 4.2994 (0.6); 4.2811 (1.5);4.2661 (2.6); 4.2573 (2.4); 4.2461 (1.4); 4.2383 (1.6); 4.2184 (0.5);3.6443 (1.0); 3.6356 (1.1); 3.6076 (2.1); 3.5982 (2.1); 3.5702 (1.1);3.5611 (1.1); 3.3361 (8.5); 3.1204 (16.0); 28898 (12.3); 2.7309 (11.2);2.6697 (0.4); 2.5464 (0.5); 2.5320 (0.4); 2.5051 (52.8); 2.5008 (69.0);2.4966 (53.0); 2.3273 (0.4); 2.2272 (0.8); 22132 (1.0); 2.2032 (1.0);2.1911 (1.0); 2.1802 (0.8); 2.1700 (0.5); 2.0712 (0.8); 2.0635 (1.0);2.0557 (1.1); 2.0404 (0.8); 2.0291 (0.7); 2.0202 (0.7); 2.0057 (0.3);−0.0003 (6.8) 483 4.51 483: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1530(3.3); 9.1331 (3.3); 8.3144 (0.4); 8.2384 (3.3); 8.2175 (3.5); 7.8013(3.3); 7.7859 (4.0); 7.7833 (4.0); 7.6663 (12.9); 7.6617 (16.0); 7.6435(3.0); 7.6257 (7.6); 7.6217 (9.8); 7.6044 (2.4); 7.3530 (3.1); 7.3342(3.3); 7.1978 (1.5); 7.1799 (3.2); 7.1626 (1.9); 7.1501 (1.9); 6.9502(2.2); 6.9325 (3.8); 6.9143 (1.8); 6.8162 (4.2); 6.7962 (3.8); 5.7539(0.9); 5.3110 (0.9); 5.2992 (1.9); 5.2910 (1.6); 5.2806 (1.9); 5.2681(0.9); 4.3430 (0.8); 4.3318 (1.2); 4.3146 (1.5); 4.3034 (1.9); 4.2377(1.5); 4.2126 (2.1); 4.1903 (1.0); 4.1861 (0.8); 3.8582 (7.3); 3.8486(9.8); 3.8372 (7.6); 3.3198 (91.4); 3.2545 (9.6); 2.8907 (1.6); 2.7317(1.5); 2.6703 (1.1); 2.5307 (28.2); 2.5057 (131.0); 2.5014 (169.2);2.4972 (132.2); 2.4303 (0.4); 2.3280 (1.0); 2.3238 (0.9); 2.2931 (0.5);2.2833 (0.7); 2.2694 (0.8); 2.2569 (1.3); 2.2474 (1.3); 2.2359 (1.1);2.2245 (1.0); 2.1036 (1.5); 20895 (1.1); 2.0744 (1.0); 2.0689 (1.0);1.3522 (0.3); 1.2983 (0.4); 1.2583 (0.6); 1.2331 (1.0); 1.0454 (0.5);1.0302 (0.5); −0.0002 (21.6) 484 1.75 484: ¹H-NMR (400.0 MHz, d₆-DMSO):δ = 9.0532 (4.3); 9.0323 (4.2); 8.5051 (0.4); 8.4393 (4.2); 8.4350(4.5); 8.4201 (4.4); 8.4155 (4.6); 8.3939 (8.8); 8.3868 (9.2); 8.3142(1.4); 7.6897 (0.4); 7.6761 (6.0); 7.6726 (6.4); 7.6560 (7.9); 7.6525(8.2); 7.6359 (2.7); 7.6087 (1.6); 7.5964 (2.8); 7.5831 (42); 7.5660(16.0); 7.5467 (7.3); 7.5290 (2.7); 7.4346 (2.4); 7.4274 (2.4); 7.4149(4.7); 7.4079 (4.6); 7.3953 (2.9); 7.3881 (2.7); 7.3083 (6.5); 7.3013(7.6); 7.2893 (5.4); 7.1723 (2.8); 7.1545 (5.6); 7.1369 (3.3); 6.9047(4.1); 6.8873 (6.8); 6.8693 (3.2); 6.7945 (7.5); 6.7740 (6.8); 5.2588(1.6); 5.2429 (3.5); 5.2246 (3.4); 5.2103 (1.5); 4.7025 (4.2); 4.6839(6.9); 4.6682 (6.4); 4.6465 (2.6); 4.6386 (2.2); 4.3431 (1.0); 4.3325(1.0); 4.2970 (6.9); 4.2829 (10.8); 4.2688 (9.9); 4.2575 (8.7); 4.2461(5.4); 4.2278 (0.8); 4.0556 (1.0); 4.0378 (3.1); 4.0200 (3.2); 4.0022(1.1); 3.7921 (5.4); 3.7775 (8.0); 3.7605 (5.6); 3.4061 (0.4); 3.3209(633.3); 3.2515 (0.4); 2.6703 (5.2); 2.5056 (663.0); 2.5013 (852.3);2.4971 (645.4); 2.3840 (0.4); 2.3324 (3.9); 2.3280 (52); 2.3082 (0.4);2.191.9 (0.8); 2.1797 (1.6); 2.1597 (1.9); 2.1448 (2.9); 2.1293 (2.4);2.1159 (1.1); 2.0312 (2.3); 2.0180 (2.4); 1.9883 (14.6); 1.2981 (0.3);1.2593 (0.4); 1.2345 (1.1); 1.1926 (3.6); 1.1748 (7.1); 1.1570 (3.5);1.0448 (6.4); 1.0295 (6.3); 0.8540 (0.3); 0.0078 (1.1); −0.0002 (31.7)485 4.61 485: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0447 (1.3); 9.0241(1.4); 8.6831 (5.0); 8.3580 (0.9); 8.3422 (1.0); 8.3344 (1.0); 8.3188(1.0); 7.6986 (1.6); 7.6939 (3.0); 7.6892 (1 8); 7.6815 (1.1); 7.6582(1.9); 7.6350 (1.0); 7.5067 (4.9); 7.5025 (4.7); 7.4296 (0.9); 7.4176(1.1); 7.4087 (1.0); 7.2865 (0.5); 7.2766 (0.9); 7.2645 (1.5); 7.2529(0.7); 7.2405 (2.7); 7.2354 (1.7); 7.2291 (1.7); 7.2245 (1.3); 7.2186(1.6); 5.5624 (0.4); 5.5433 (1.1); 5.5237 (1.1); 5.5041 (0.4); 3.8775(2.7); 3.8671 (4.2); 3.8565 (2.8); 3.5679 (2.1); 3.3194 (17.3); 3.2870(3.4); 3.2784 (3.4); 3.0030 (0.3); 2.9938 (0.4); 2.9851 (0.5); 2.9765(0.6); 2.9634 (0.6); 2.9552 (0.5); 2.9048 (0.4); 2.8845 (0.9); 2.8646(0.7); 2.8450 (0.5); 2.6708 (0.5); 2.6662 (0.4); 2.5661 (0.3); 2.5564(0.6); 2.5453 (0.8); 2.5356 (1.0); 2.5237 (2.6); 2.505S 1 (67.0); 2.5015(85.5); 2.4972 (64.1); 2.3327 (0.4); 2.3285 (0.5); 2.3238 (0.4); 1.9882(1.2); 1.9554 (0.6); 1.9449 (0.3); 1.9351 (0.6); 1.9237 (0.6); 1.9042(0.6); 1.3978 (16.0); 1.1752 (0.6); −0.0002 (3.5) 486 2.63 486: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.3542 (5.2); 9.3302 (5.6); 9.1745 (3.3);9.1546 (3.4); 8.5530 (16.0); 8.4199 (3.0); 8.4043 (3.3); 8.3963 (3.5);8.3808 (3.2); 8.1903 (5.9); 8.1702 (6.4); 7.7341 (3.5); 7.7112 (6.5);7.6943 (2.1); 7.6878 (5.3); 7.6762 (3.0); 7.6661 (2.0); 7.6563 (1.7);7.5069 (2.7); 7.4864 (3.7); 7.4659 (2.1); 7.345 (4.0); 7.3267 (4.4);7.1685 (2.0); 7.1506 (4.3); 7.1329 (2.6); 7.1302 (2.5); 6.9072 (3.0);6.8889 (5.2); 6.8703 (2.4); 6.7892 (5.9); 6.7690 (5.4); 5.2557 (1.2);5.2415 (2.6); 5.2224 (2.7); 5.2081 (15); 4.2961 (0.7); 4.2873 (1.0);4.2804 (0.9); 4.2686 (2.4); 4.2592 (2.3); 4.2526 (2.8); 4.2429 (3.4);4.2350 (2.7); 4.2211 (2.2); 4.2140 (2.8); 4.1933 (1.0); 4.1864 (0.8);4.0381 (0.5); 4.0204 (0.5); 3.8901 (13.8); 3.8786 (8.0); 3.8613 (1.1);3.3619 (1.0); 3.3512 (1.8); 3.3217 (51.2); 3.3073 (9.9); 3.2947 (4.6);3.2752 (1.7); 3.2647 (1.0); 2.6702 (0.9); 2.6662 (0.7); 2.5404 (3.4);2.5054 (114.7); 2.5012 (147.6); 2.4969 (111.5); 2.3277 (0.9); 2.2413(0.6); 2.2284 (0.9); 2.2203 (1.2); 2.2072 (1.7); 2.1979 (1.7); 2.1856(1.8); 2.1736 (1.3); 2.1643 (0.8); 2.0621 (1.2); 2.0540 (1.7); 2.0471(1.9); 2.0314 (1.4); 2.0198 (1.3); 2.0125 (1.2); 2.0049 (0.8); 1.9975(0.6); 1.9883 (2.2); 1.2586 (0.4); 1.2350 (0.4); 1.1927 (0.6); 1.1749(1.1); 1.1589 (5.2); 1.0697 (4.9); 1.0455 (0.4); 1.0301 (0.4); 0.1459(0.7); 0.0073 (6.8); −0.0002 (147.2); −0.1497 (0.8) 490 2.96 490: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.1477 (4.1); 9.1276 (4.1); 8.5827 (12.2);8.3171 (2.9); 8.3016 (3.0); 8.2939 (3.1); 8.2782 (2.8); 7.9206 (2.2);7.6395 (3.1); 7.6171 (5.3); 7.5945 (2.9); 7.3628 (2.2); 7.3551 (2.2);7.3452 (2.4); 7.3386 (2.3); 7.2276 (2.8); 7.2178 (2.4); 7.2081 (3.6);7.1982 (3.5); 7.1819 (2.0); 7.1787 (2.0); 7.1607 (4.1); 7.1434 (6.7);7.1244 (2.7); 7.0096 (0.5); 6.9931 (0.7); 6.9503 (3.6); 6.9211 (5.0);6.9062 (4.3); 6.8877 (2.0); 6.7966 (5.4); 6.7764 (4.8); 5.2635 (1.1);5.2495 (2.4); 5.2301 (2.4); 5.2154 (1.1); 4.2964 (0.9); 4.2773 (2.1);4.2608 (2.5); 4.2515 (2.8); 4.2266 (2.2); 4.1995 (0.8); 4.0557 (1.2);4.0379 (3.4); 4.0201 (3.4); 4.0023 (1.1); 3.8713 (11.2); 3.3206 (387.1);3.2966 (7.4); 3.2905 (7.5); 3.2825 (7.0); 3.2732 (5.1); 3.2568 (2.4);3.2395 (1.2); 2.6747 (1.8); 2.6703 (2.4); 2.6661 (1.8); 2.5057 (315.1);2.5013 (404.4); 2.4970 (301.6); 2.4284 (0.4); 2.3278 (5.0); 2.2944(14.1); 2.2808 (14.3); 2.2321 (3.2); 2.2139 (1.4); 2.2024 (1.5); 2.1933(1.5); 2.1807 (1.2); 2.0542 (1.7); 2.0257 (1.2); 2.0200 (1.1); 2.0040(0.6); 1.9883 (14.3); 1.8912 (14.0); 1.8683 (13.8); 1.3979 (16.0);1.2586 (0.3); 1.2359 (0.8); 1.1927 (3.8); 1.1749 (7.5); 1.1571 (3.7);1.0448 (0.8); 1.0296 (0.8); −0.0002 (5.2) 515 3.00 515: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 9.1233 (0.6); 9.1025 (0.6); 8.5606 (1.9); 8.2915(0.5); 8.2868 (0.5); 8.2717 (0.5); 8.2669 (0.5); 8.1363 (10.5); 7.7032(0.6); 7.6996 (0.6); 7.6S3 2 (0.8); 7.6797 (0.7); 7.6686 (0.8); 7.6482(1.2); 7.6420 (0.9); 7.4385 (0.4); 7.4299 (0.4); 7.3534 (0.6); 7.3361(0.7); 7.1628 (0.5); 7.1460 (0.3); 7.1422 (0.3); 6.9168 (0.4); 6.8993(0.6); 6.7981 (0.7); 6.7787 (0.6); 4.2597 (0.6); 4.2485 (0.5); 4.2391(0.3); 3.8361 (0.4); 3.8217 (0.4); 3.8088 (0.5); 3.3351 (2.2); 3.3298(2.2); 3.3070 (2.3); 3.1311 (0.5); 3.1135 (0.7); 3.0824 (4.2); 2.6708(0.4); 2.5061 (48.0); 2.5017 (62.2); 2.4973 (46.5); 2.3283 (0.4); 2.0857(16.0); 2.0411 (0.4); 2.0329 (0.4); 1.7082 (0.4); −0.0002 (7.0) 516 3.90516: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.8758 (2.0); 8.8723 (2.0); 8.8550(2.1); 8.7191 (6.4); 8.7148 (6.2); 8.3524 (1.2); 8.3445 (1.3); 8.3368(1.4); 8.3289 (2.5); 8.3210 (1.5); 8.3134 (1.4); 8.3055 (1.3); 7.7689(2.3); 7.7459 (4.2); 7.7227 (2.4); 7.7125 (0.7); 7.7045 (0.7); 7.6975(1.2); 7.6926 (1.2); 7.6839 (1.1); 1.6712 (1.2); 7.6640 (0.7); 7.6561(0.6); 7.6484 (0.5); 7.4239 (1.8); 7.4047 (1.9); 7.3115 (0.8); 7.2995(1.1); 7.2892 (1.4); 7.2665 (0.7); 7.1748 (1.3); 7.1716 (1.4); 7.1539(2.8); 7.1364 (1.7); 7.1330 (1.7); 6.9314 (2.0); 6.9130 (3.4); 6.8946(1.6); 6.7840 (3.8); 6.7652 (3.4); 5.2246 (0.7); 5.2093 (1.6); 5.1923(1.6); 5.1773 (0.6); 4.2981 (0.4); 4.2901 (0.6); 4.2828 (0.5); 4.2711(1.6); 4.2620 (1.6); 4.2542 (2.4); 4.2456 (2.6); 4.2255 (1.6); 4.2200(1.2); 4.2049 (0.4); 4.1983 (0.5); 4.0560 (0.4); 4.0382 (1.3); 4.0204(1.3); 4.0027 (0.5); 3.5003 (16.0), 3.4938 (15.3); 3.4796 (0.6); 3.3204(13.4); 3.2904 (24.9); 3.2554 (0.4); 2.6753 (0.4); 2.6707 (0.6); 2.6667(0.4); 2.5061 (71.2); 2.5017 (92.2); 2.4972 (69.1); 2.3327 (0.4); 2.3285(0.5); 2.3241 (0.4); 2.1784 (0.7); 2.1686 (0.8); 2.1561 (1.0); 2.1492(1.0); 2.1437 (1.0); 2.1362 (0.8); 2.0592 (0.7); 2.0512 (0.9); 2.0433(1.2); 2.0354 (1.1); 2.0257 (0.9); 2017 8 (0.8); 2.0087 (0.8); 20018(0.7); 1.9887 (6.0); 1.3975 (4.4); 1.1929 (1.5); 1.1751 (3.0); 1.1573(1.4); 0.0079 (0.5); −0.0002 (12.2); 0.0082 (0.5) 518 2.19 518: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.0894 (1.9); 9.0689 (1.9); 8.5253 (6.9);8.4176 (1.8); 8.3983 (2.0); 7.9524 (2.4); 7.7616 (2.1); 7.7592 (2.1);7.7438 (2.6); 7.7414 (2.4); 7.7153 (0.8); 7.7027 (1.6); 7.6900 (0.8);7.6238 (6.7); 7.6194 (12.3); 7.6103 (4.6); 7.6061 (3.5); 7.6009 (1.5);7.5766 (1.8); 7.5583 (2.0); 7.5555 (2.0); 7.5374 (1.5); 7.3313 (1.8);7.3134 (1.9); 7.1897 (0.9); 7.1870 (0.8); 7.1692 (1.8); 7.1516 (1.2);7.1480 (1.1); 6.9265 (1.3); 6.9239 (1.3); 6.9076 (2.2); 6.8894 (1.1);6.8867 (1.0); 6.8100 (2.5); 6.7896 (2.3); 5.2760 (0.5); 5.2619 (1.1);5.2426 (1.1); 5.2280 (0.5); 4.6943 (1.5); 4.6787 (2.2); 4.6755 (2.2);4.6691 (1.7); 4.6600 (1.9); 4.6536 (2.3); 4.6505 (2.1); 4.6349 (1.6);4.3095 (0.3); 4.2989 (1.9); 4.2902 (3.4); 4.2843 (4.8); 4.2753 (5.3);4.2612 (3.2); 3.8016 (1.6); 3.7850 (2.6); 3.7698 (1.8); 3.3394 (0.5);3.3204 (30.7); 3.3072 (1.3); 32882 (0.7); 3.2737 (0.4); 2.8904 (16.0);2.7318 (13.8); 2.6 747 (0.4); 2.6701 (0.5); 2.6659 (0.4); 2.5058 (64.7);2.5014 (82.8); 2.4969 (60.3); 2.4927 (29.6); 2.3281 (0.5); 2.1972 (0.4);2.1851 (0.4); 2.1757 (0.6); 2.1616 (0.9); 2.1460 (0.7); 2.1320 (0.3);2.0740 (2.6); 2.0620 (0.8); 2.0505 (0.8); 2.0356 (0.6); 2.0263 (0.6);2.0164 (0.5); 0.0079 (1.5); −0.0002 (38.6); −0.0085 (1.5) 522 2.88 522:¹H-NMR (601.6 MHz, d₆-DMSO): δ = 9.0428 (0.8); 9.0296 (0.8); 8.1535(0.8); 8.1513 (0.8); 8.1394 (0.9); 8.1372 (0.9); 7.7631 (0.8); 7.7608(0.8); 7.7512 (1.0); 7.7490 (0.9); 7.6672 (3.5); 7.6640 (3.9); 7.6101(0.9); 7.6069 (1.5); 7.6038 (0.7); 7.5892 (0.8); 7.5772 (0.8); 7.5752(0.8); 7.5632 (0.7); 7.3301 (0.6); 7.3172 (0.7); 7.1857 (0.4); 7.1831(0.4); 7.1716 (0.7); 7.1600 (0.4); 7.1574 (0.4); 6.9397 (0.5); 6.9380(0.5); 6.9257 (0.8); 6.9149 (0.4); 6.9132 (0.4); 6.8047 (0.9); 7924(0.9); 5.7502 (1.4); 5.2771 (0.4); 5.2642 (0.4); 4.2903 (0.4); 4.2268(0.3); 4.2106 (0.5); 3.3053 (4.6); 3.0336 (16.0); 2.5150 (7.7); 2.5060(4.4); 2.5030 (9.2); 2.5000 (12.7); 2.4970 (9.2); 2.4940 (4.3); 1.3973(0.8); −0.0002 (9.1) 523 2.11 523: ¹H-NMR (601.6 MHz, d₆-DMSO): δ =9.0676 (0.4); 9.0547 (0.6); 9.0421 (0.3); 8.1664 (0.9); 8.1630 (0.9);8.1534 (1.1); 8.1499 (1.0); 7.6767 (1.1); 7.6741 (1.1); 7.6632 (1.3);7.6607 (1.2); 7.5844 (0.6); 7.5726 (1.4); 7.5593 (2.3); 7.5550 (1.3);7.5467 (0.4); 7.4260 (0.6); 7.4174 (0.4); 7.3207 (0.5); 7.3128 (0.9);7.3014 (1.2); 7.1740 (0.4); 7.1635 (0.8); 7.1501 (0.4); 6.9255 (0.4);6.9132 (0.5); 6.7968 (1.0); 6.7823 (0.9); 5.3055 (0.4); 5.2630 (0.4);5.2568 (0.4); 4.2883 (0.4); 4.2826 (0.4); 4.2086 (0.4); 4.1667 (0.4);3.3028 (42.7); 3.0387 (16.0); 3.0127 (0.7); 2.6147 (0.4); 2.6116 (0.5);2.6084 (0.4); 2.6054 (0.5); 2.5208 (0.9); 2.5178 (1.1); 2.5147 (1.2);2.5059 (28.6); 2.5029 (63.1); 2.4999 (88.1); 2.4968 (63.1); 2.4938(29.0); 24136 (4.2); 2.3869 (0.4); 2.3840 (0.5); 2.3811 (0.4); 2.2183(0.4); 2.2113 (0.4); 1.3983 (11.6); 0.0052 (1.4); −0.0002 (61.6);−0.0058 (2.3) 524 2.34 524: ¹H-NMR (601.6 MHz, d₆-DMSO): δ = 9.0713(0.8); 9.0578 (0.8); 8.1990 (0.9); 8.1846 (0.9); 7.7017 (0.8); 7.6914(1.0); 7.6896 (1.0); 7.6095 (0.9); 7.5972 (1.0); 7.5837 (0.8); 7.5631(0.4); 7.3217 (0.8); 7.3096 (0.8); 7.1789 (0.8); 7.1680 (1.0); 7.1566(0.6); 6.9311 (0.6); 6.9192 (1.0); 6.9080 (0.6); 6.8015 (1.0); 6.7876(0.9); 5.2704 (0.6); 5.2579 (0.5); 4.3124 (0.4); 4.3049 (0.4); 4.2890(0.4); 4.2232 (0.5); 4.2075 (0.5); 4.1930 (0.3); 4.1891 (0.4); 3.3025(59.1); 3.2911 (0.4); 3.0396 (16.0); 3.0127 (0.9); 2.6120 (0.9); 2.6084(0.7); 2.6057 (0.8); 2.5210 (1.5); 2.5180 (1.8); 2.5145 (1.8); 2.5058(51.6); 2.5030 (107.0); 2.5000 (145.0); 2.4970 (104.8); 2.4942 (49.6);2.4679 (7.8); 2.3842 (1.0); 2.2364 (0.4); 2.2282 (0.3); 2.2188 (0.4);2.0703 (0.4); 1.3984 (0.7); 1.2362 (0.8); 0.0966 (0.4); 0.0052 (2.0);−0.0002 (82.2); −0.0057 (3.6); −0.1001 (0.5) 525 2.62 525: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 9.1140 (1.1); 9.1057 (1.1); 9.0945 (1.2); 9.0855(1.0); 8.5540 (6.4); 8.3143 (0.7); 8.2423 (1.9); 8.2373 (1.8); 8.2225(2.0); 8.2176 (2.0); 7.7020 (2.3); 7.6983 (2.3); 7.6822 (3.5); 7.6783(2.8); 7.6659 (3.1); 7.6457 (5.0); 7.6395 (3.2); 7.6264 (1.0); 7.4582(0.8); 7.4470 (0.9); 7.4388 (1.7); 7.4279 (1.6); 7.4191 (1.1); 7.4078(0.9); 7.3495 (2.8); 7.3293 (3.4); 7.3094 (0.8); 7.1767 (1.0); 7.1592(2.0); 7.1411 (1.3); 6.9254 (1.4); 6.9072 (2.4); 6.8882 (1.1); 6.7955(2.8); 6.7753 (2.5); 5.2371 (1.1); 5.2227 (1.1); 4.2896 (0.5); 4.2708(1.3); 4.2555 (2.3); 4.2473 (2.1); 4.2358 (1.2); 4.2282 (1.4); 4.2078(0.4); 4.2005 (0.3); 3.5676 (0.3); 3.3679 (1.4); 3.3498 (4.3); 3.3208(300.6); 3.0155 (14.3); 2.6749 (1.8); 2.6704 (2.3); 2.6663 (1.7); 2.5234(7.5); 2.5058 (309.0); 2.5014 (394.8); 2.4970 (286.9); 2.3325 (1.8);2.3280 (2.3); 2.3240 (1.7); 2.2142 (0.5); 2.2047 (0.5); 2.1922 (0.8);2.1823 (0.8); 2.1699 (0.8); 2.1586 (0.6); 2.1484 (0.4); 2.0360 (0.8);2.0218 (0.7); 2.0092 (0.6); 2.0012 (0.6); 1.9885 (0.8); 1.3979 (16.0);1.2461 (3.0); 1.22 88 (6.1); 1.2111 (3.0); 1.1924 (0.3); 1.1750 (0.4);−0.0002 (1.8) 526 3.29 526: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1145(1.7); 9.0942 (1.7); 8.5403 (7.4); 8.1746 (1.7); 8.1548 (1.8); 7.6988(2.3); 7.6951 (2.4); 7.6788 (2.9); 7.6748 (3.6); 7.6559 (2.9); 7.6357(3.6); 7.6280 (3.1); 7.6136 (1.0); 7.4537 (0.9); 7.4429 (0.9); 7.4343(1.8); 7.4235 (1.7); 7.4147 (1.2); 7.4039 (1.0); 7.3536 (3.2); 7.3346(3.1); 7.30831 (0.9); 7.3051 (0.8); 7.1757 (1.0); 7.1569 (2.0); 7.1382(1.2); 6.9241 (1.2); 6.9056 (2.1); 6.8868 (1.0); 6.7922 (2.8); 6.7720(2.5); 5.7549 (1.2); 5.2457 (0.5); 5.2315 (12); 5.2132 (1.2); 5.1980(0.5); 4.2829 (0.5); 4.2761 (0.4); 4.2640 (12); 4.2546 (1.2); 4.2470(1.8); 4.2373 (1.9); 4.2238 (1.1); 4.2164 (1.3); 4.1962 (0.4); 4.1885(0.4); 3.9291 (0.3); 3.9131 (0.8); 3.8976 (1.1); 3.8822 (0.8); 3.8664(0.4); 3.5675 (0.5); 3.3231 (30.0); 2.9033 (1 6.0); 2.5054 (39.1);2.5010 (51.0); 2.4966 (38.0); 2.2017 (0.4); 2.1928 (0.5); 2.1801 (0.8);2.1703 (0.8); 2.1590 (0.8); 2.1480 (0.6); 2.1392 (0.4); 2.0400 (0 6);2.0328 (0.8); 2.0253 (0.9); 2.0145 (0.7); 2.0089 (0.7); 1.9987 (0.6);1.9884 (0 8); 1.3068 (3.5); 1.2921 (5.6); 1.2777 (3.4); 1.2512 (3.4);1.2373 (5.5); 1.2230 (3.7) 527 3.63 527: ¹H-NMR (400.0 MHz, d₆-DMSO): δ= 9.1286 (1.0); 9.1083 (1.1); 8.6686 (4.7); 8.4516 (3.2); 8.2373 (1.1);8.2341 (1.1); 8.2161 (1.3); 8.2128 (1.2); 7.8200 (1.1); 7.8167 (1.2);7.8022 (1.5); 7.7989 (1.4); 7.7348 (2.1); 7.7297 (2.4); 7.6837 (1.2);7.6655 (12); 7.6626 (1.3); 7.6443 (2.1); 7.6384 (11.9); 7.6320 (2.0);7.3779 (1.0); 7.3 605 (1.1); 7.1943 (0.5); 7.1905 (0.5); 7.1728 (1.0);7.1559 (0.7); 7.1521 (0.6); 6.9502 (0.7); 6.9476 (0.8); 6.9293 (1.3);6.9130 (0.6); 6.9103 (0.6); 6.8094 (1.4); 6.8075 (1.4); 6.7889 (1.4);5.2566 (0.7); 5.2372 (0.7); 4.2852 (0.6); 4.2699 (12); 4.2609 (1.1);4.2491 (0.6); 4.2412 (0.7); 3.3594 (0.7); 3.3415 (2.2); 3.3200 (56.0);3.0101 (9.2); 2.6752 (0.5); 2.6706 (0.7); 2.6662 (0.5); 2.5237 (2.3);2.5103 (47.2); 2.5060 (93.7); 2.5015 (122.2); 2.4970 (89.4); 2.4929(452); 2.3326 (0.6); 2.3283 (0.7); 2.3238 (0.6); 2.2063 (0.4); 2.1961(0.4); 2.1845 (0.5); 2.1724 (0.3); 2.0710 (0.4); 2.0632 (0.5); 2.0484(0.4); 2.0365 (0.3); 1 3978 (16.0); 1.2311 (2.6); 1.2134 (5.1); 1.1956(2.2); −0.0002 (0.5) 534 4.51 534: ¹H-NMR (400.0 MHz, d₆-DMSO): δ =10.4184 (1.5); 9.1346 (1.4); 9.1144 (1.4); 8.6595 (5.5); 8.1798 (1.4);8.1587 (1.5); 7.8117 (1.4); 7.7965 (1.8); 7.7941 (1.7); 7.7032 (0.5);7.681 5 (1.4); 7.6605 (1.7); 7.6458 (10.6); 7.3875 (1.3); 7.3689 (1.4);7.1966 (0.6); 7.1784 (1.4); 7.1608 (0.9); 6.9817 (0.5); 6.9771 (0.9);6.9724 (0.5); 6.9544 (1.0); 6.9360 (1.6); 6.9173 (0.8); 6.8121 (1.9);6.8008 (2.0); 6.7960 (2.5); 5.2728 (0.4); 5.2584 (0.8); 5.2391 (0.9);5.2247 (0.4); 4.2869 (0.8); 4.2708 (1.1); 4.2589 (1.1); 4.2454 (0.7);4.2376 (0.9); 3.8866 (0.7); 3.8705 (1.0); 3.8538 (0.7); 3.3288 (47.9);2.9128 (10.7); 2.6782 (0.6); 2.5136 (82.9); 2.5093 (107.6); 2.5050(80.2); 23403 (0.5); 2.3361 (0.6); 2.3319 (0.5); 22178 (0.4); 2.2040(0.5); 2.1942 (0.6); 2.1821 (0.6); 2.1704 (0.5); 2.0675 (0.5); 2.0600(0.6); 2.0439 (0.5); 2.0335 (0.4); 2.0261 (0.4); 1.4053 (16.0); 1.2887(5.0); 1.2725 (5.0); 1.2420 (5.3); 1.2258 (5.0) 535 4.46 535: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 8.8722 (0.8); 8.8516 (0.8); 8.7041 (2.9);8.2580 (1.2); 8.2352 (1.4); 7.8664 (1.4); 7.8435 (1.3); 7.6619 (3.4);7.4145 (0.7); 7.3959 (0.8); 7.1707 (0.4); 7.1537 (0.7); 7.1329 (0.4);6.9285 (0.5); 6.9101 (0.9); 6.8908 (0.4); 6.7836 (1.0); 6.7635 (0.9);5.2026 (0.5); 5.1839 (0.5); 4.2665 (0.4); 4.25 83 (0.4); 4.2499 (0.6);4.2428 (0.6); 4.2229 (0.4); 4.2156 (0.5); 3.4842 (7.0); 3.3198 (29.6);3.2787 (6.2); 2.6708 (0.3); 2.5056 (44.2); 2.5014 (56.4); 2.4974 (43.0);2.3286 (0.3); 2.0317 (0.4); 1.9886 (0.5); 1.3980 (16.0); −0.0003 (15.4)540 3.72 540: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1842 (4.4); 9.1640(4.4); 8.6741 (16.0); 8.4617 (0.4); 8.3556 (3.0); 8.3401 (3.2); 8.3321(3.3); 8.3164 (3.3); 7.6826 (3.4); 7.6594 (6.4); 7.636 2 (3.2); 7.4662(4.8); 7.4486 (5.5); 7.4447 (5.5); 7.4269 (4.5); 7.3795 (4.1); 7.3605(4.4); 7.1914 (2.0); 7.1887 (2.0); 7.1711 (4.2); 7.1530 (2.6); 7.1500);(2.5); 6.9408 (3.0); 6.9222 (5.1); 6.9035 (2.4); 6.8037 (5.7); 6.7840(5.1); 5.2738 (1.2); 5.2596 (2.6); 5.2405 (2.6); 5.2262 (1.1); 4.3027(1.0); 4.2958 (0.9); 4.2846 (2.4); 4.2751 (2.3); 4.2681 (2.8); 4.2591(3.5); 4.2517 (2.7); 4.2384 (2.1); 4.2312 (2.7); 4.2103 (1.0); 4.2029(0.8); 4.0555 (0.7); 4.0377 (1.9); 4.0199 (1.9); 4.0021 (0.7); 3.9008(1.0); 3.8822 (8.3); 3.8717 (14.3); 3.8610 (8.7); 3.3197 (180.6); 3.2906(5.5); 3.2801 (11.1); 3.2687 (10.7); 3.2580 (4.7); 3.2387 (1.4); 2.6745(1.6); 2.6702 (2.1); 2.5055 (277.9); 2.5013 (357.7); 2.4970 (267.8);2.3321 (1.6); 2.3279 (2.2); 2.255 3 (0.6); 2.2451 (0.9); 2.2347 (12);2.2216 (1.7); 2.2121 (1.8); 2.1999 (1.8); 2.1877 (1.3); 2.1789 (0.8);2.0746 (1.6); 2.0676 (1.9); 2.0556 (1.4); 2.0399 (1.3); 2.0329 (1.2);1.9863 (8.1); 1.3978 (1.0); 1.2592 (0.3); 1.2341 (0.8); 1.1926 (2.1);1.1748 (4.1); 1.1569 (2.1); −0.0002 (42.6) 541 1.78 541: ¹H-NMR. (400.0MHz, d₆-DMSO): δ = 8.9748 (0.6); 8.9542 (0.6); 8.4871 (0.4); 8.4708(2.2); 8.4638 (0.5); 8.4484 (0.4); 8.3359 (2.1); 7.9088 (0.3); 7.8960(0.4); 7.7294 (0.7); 7.7258 (0.8); 7.7093 (0.9); 7.7057 (0.9); 7.5431(0.5); 7.5208 (0.8); 7.4979 (0.5); 7.4693 (0.5); 7.4610 (0.4); 7.4497(1.0); 7.4300 (0.6); 7.3462 (0.3); 7.3415 (0.5); 7.3365 (0.4); 7.3272(1.1); 7.3228 (0.7); 7.3076 (0.8); 7.3033 (1.1); 7.2820 (0.7); 7.1749(0.3); 7.1716 (0.3); 7.1539 (0.7); 7.1363 (0.4); 7.1330 (0.4); 6.9111(0.5); 6.8923 (0.8); 6.8739 (0.4); 6.7934 (0.9); 6.7732 (0.8); 5.2315(0.4); 5.2128 (0.4); 4.2613 (0.7); 4.2476 (1.2); 4.2347 (0.7); 3.3288(21.4); 3.0736 (2.0); 3.0669 (1.4); 3.0611 (2.2); 2.5180 (17.5); 2.5140(34.2); 2.5095 (44.3); 2.5051 (32.0); 2.1427 (0.3); 2.0180 (0.3); 1.9968(0.9); 1.4060 (16.0); 1.2437 (0.4); 1.1831 (0.4) 542 1.66 542: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 8.9915 (1.7); 8.9705 (1.8); 8.5165 (1.4);8.5013 (1.5); 8.4929 (1.5); 8.4778 (1.3); 8.3922 (7.2); 7.9585 (0.8);7.9451 (1.0); 7.9379 (1.0); 7.9251 (0.8); 7.6623 (0.4); 7.6538 (0.5);7.6394 (0.9); 7.6341 (0.9); 7.6261 (0.9); 7.6139 (0.9); 7.5986 (0.5);7.5902 (0.4); 7.5685 (1.5); 7.5457 (2.8); 7.5228 (1.5); 7.3069 (1.8);7.2877 (2.0); 7.2267 (0.6); 7.2113 (0.8); 7.2049 (1.0); 7.1995 (1.0);7.1755 (1.5); 7.1717 (1.5); 7.1544 (2.2); 7.1367 (1.4); 7.1332 (1.2);6.9136 (1.5); 6.8949 (2.6); 6.8763 (1.2); 6.7934 (3.0); 6.7729 (2.8);5.7556 (16.0); 5.2463 (0.6); 5.2312 (1.4); 5.2118 (1.4); 5.1972 (0.6);4.2576 (2.0); 4.2458 (3.6); 4.2342 (2.0); 4.0382 (0.6); 4.0204 (0.6);3.3231 (35.1); 3.0726 (4.9); 3.0657 (6.0); 3.0603 (5.8); 3.0534 (4.9);2.6753 (0.3); 2.6706 (0.4); 2.5103 (28.6); 2.5062 (55.4); 2.5017 (70.8);2.4972 (50.6); 2.3286 (0.4); 2.1779 (0.8); 2.1644 (0.8); 2.1576 (0.7);2.1428 (1.0); 2.1289 (1.0); 2.1160 (0.4); 2.0254 (0.8); 2.0189 (0.8);2.0043 (0.7); 1.9887 (3.0); 1.3974 (0.6); 1.3525 (0.5); 1.2988 (0.3);1.2590 (0.5); 1.2344 (1.2); 1.1928 (0.7); 1.1750 (1.4); 1.1572 (0.7);0.0079 (1.9); −0.0002 (47.9); −0.0085 (1.8) 543 4.25 543: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 9.1849 (4.4); 9.1647 (4.3); 8.7031 (1.0); 8.6905(16.0); 8.6712 (0.7); 8.3740 (3.5); 8.3584 (3.8); 8.3503 (3.9); 8.3348(3.6); 8.3149 (0.5); 7.6836 (3.9); 7.6607 (7.1); 7.6380 (3.7); 7.6243(0.4); 7.3846 (4.1); 7.3651 (4.7); 7.2348 (0.5); 7.2223 (4.0); 7.1898(5.8); 7.1718 (5.0); 7.1540 (3.1); 7.1505 (2.8); 6.9435 (3.5); 6.9267(5.9); 6.9083 (2.7); 6.8046 (6.4); 6.7845 (5.9); 6.7131 (0.4); 5.7551(0.4); 5.2587 (2.7); 5.2416 (2.7); 5.2278 (1.2); 4.3052 (1.2); 4.2978(1.1); 4.2860 (2.8); 4.2761 (2.8); 4.2697 (3.2); 4.2611 (3.9); 4.2528(2.9); 4.2390 (2.5); 4.2324 (3.0); 4.2105 (1.1); 4.2039 (0.9); 4.0559(0.6); 4.0377 (1.8); 4.0200 (1.8); 4.0019 (0.6); 3.8664 (15.1); 3.3202(106.3); 3.2860 (10.0); 3.2751 (9.5); 2.6740 (1.4); 2.6705 (1.8); 2.6660(1.4); 2.5055 (243.9); 2.5012 (311.2); 2.4968 (223.6); 2.3279 (1.8);2.3233 (1.3); 2.2376 (1.3); 2.2238 (1.9); 2.2145 (2.0); 2.2028 (2.0);2.1943 (1.4); 2.1895 (1.5); 2.0685 (1.8); 2.0522 (1.6); 1.9883 (7.3);1.3976 (5.4); 1.3510 (0.4); 1.2985 (0.4); 1.2588 (0.4); 1.2354 (1.3);1.1925 (1.9); 1.1747 (3.9); 1.1568 (1.8); 0.1464 (0.7); 0.0222 (0.4);0.0079 (6.3); −0.0002 (153.6); −0.0085 (5.8); −0.1493 (0.7) 544 2.80544: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1606 (3.0); 9.1401 (3.1); 8.6477(12.1); 8.2912 (2.2); 8.2755 (2.4); 8.2676 (2.5); 8.2521 (2.3); 7.6215(2.5); 7.5986 (4.5); 7.5757 (2.5); 7.3791 (2.8); 7.3620 (3.0); 7.1920(1.4); 7.1885 (1.4); 7.1709 (2.9); 7.1534 (1.8); 7.1497 (1.7); 6.9443(2.1); 6.9421 (2.1); 6.9256 (3.6); 6.9236 (3.5); 6.9073 (1.7); 6.9047(1.7); 6.8055 (4.1); 6.7851 (3.8); 6.6355 (2.1); 5.7553 (12.7); 5.2771(0.8); 5.2633 (1.8); 5.2443 (1.8); 5.2300 (0.8); 4.3146 (0.5); 4.3063(0.7); 4.2990 (0.6); 4.2870 (1.6); 4.2781 (1.6); 4.2711 (2.0); 4.2624(2.4); 4.2554 (1.9); 4.2420 (1.5); 4.2344 (1.9); 4.2136 (0.7); 4.2060(0.5); 3.8626 (9.5); 3.8532 (5.6); 3.8342 (0.7); 3.8221 (0.4); 3.3200(38.5); 3.2903 (3.2); 3.2796 (6.3); 3.2671 (6.0); 3.2350 (1.0); 2.6787(0.3); 2.6702 (0.8); 2.5231 (2.6); 2.5097 (54.0); 2.5055 (106.3); 2.5010(136.5); 2.4965 (96.8); 2.4922 (46.2); 2.4203 (16.0); 2.3242 (1.1);2.2576 (0.5); 2.2436 (0.7); 2.2357 (0.9); 2.2233 (1.1); 2.2137 (1.2);2.2007 (1.2); 2.1894 (0.9); 2.1807 (0.6); 2.0829 (7.5); 2.0400 (1.0);2.0318 (0.8); 2.0158 (0.4); 1.9882 (0.8); 1.5432 (0.7); 1.3973 (1.0);1.3513 (0.4); 1.2587 (0.5); 1.2336 (0.9); 1.1746 (0.4); 0.1459 (0.4);0.0079 (3.7); −0.0002 (97.6); −0.0085 (3.4); −0.1493 (0.4) 545 1.90 545:¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0012 (2.2); 8.9809 (2.3); 8.5133(1.7); 8.4986 (1.6); 8.4897 (1.6); 8.4749 (1.4); 8.4325 (7.9); 8.2292(0.6); 8.0071 (1.3); 7.9948 (1.2); 7.6863 (14.1); 7.5760 (1.7); 7.5526(3.2); 7.5293 (1.7); 7.3076 (2.2); 7.2888 (2.2); 7.1799 (1.0); 7.1765(1.2); 7.1589 (2.2); 7.1414 (1.4); 7.1380 (1.3); 6.9211 (1.7); 6.9184(1.6); 6.9022 (2.7); 6.8999 (2.7); 6.8839 (1.3); 6.8811 (1.3); 6.8673(3.0); 6.8082 (0.3); 6.7983 (3.0); 6.7961 (3.0); 6.7779 (2.8); 6.7756(2.6); 5.7552 (16.0); 5.2468 (0.7); 5.2319 (1.5); 5.2124 (1.4); 5.1971(0.6); 4.2623 (2.5); 4.2494 (4.1); 4.2359 (2.4); 4.0381 (0.9); 4.0202(1.0); 3.3223 (44.4); 3.0701 (8.6); 3.0576 (8.5); 3.0357 (0.8); 2.6753(0.4); 2.6709 (0.6); 2.6665 (0.4); 2.5106 (38.2); 2.5063 (75.6); 2.5018(97.9); 2.4973 (70.3); 2.4929 (33.9); 2.3332 (0.4); 2.3285 (0.6); 2.3240(0.4); 2.1939 (0.3); 2.1795 (0.8); 2.1646 (0.8); 2.1595 (0.7); 2.1436(1.1); 2.1303 (1.0); 2.1160 (0.4); 2.0570 (0.5); 2.0446 (1.0); 2.0307(1.2); 2.0172 (0.7); 2.0089 (0.8); 1.9887 (4.5); 1.2590 (0.4); 1.2335(0.7); 1.1928 (1.2); 1.1750 (2.3); 1.1573 (1.2); −0.0002 (3.4) 546 3.68546: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1871 (4.2); 9.1669 (4.3); 8.6805(16.0); 8.3627 (2.8); 8.3473 (3.0); 8.3393 (3.2); 8.3236 (2.9); 7.6904(3.2); 7.6672 (6.0); 7.6441 (3.1); 7.539 4 (2.8); 7.4347 (8.4); 7.4122(8.4); 7.3793 (3.9); 7.3591 (9.8); 7.1913 (2.0); 7.1880 (2.1); 7.1785(3.6); 7.1709 (4.1); 7.1531 (2.5); 7.1496 (2.3); 6.9405 (2.8); 6.9219(4.7); 6.9054 (2.3); 6.9030 (2.3); 6.8038 (5.3); 6.7850 (4.9); 5.7551(10.2); 5.2756 (1.1); 5.2613 (2.4); 5.2412 (2.4); 5.2271 (1.1); 4.3122(0.6); 4.3044 (1.0); 4.2852 (2.2); 4.2768 (2.1); 4.2686 (2.6); 4.2604(3.2); 4.2535 (2.5); 4.2393 (2.0); 4.2322 (2.6); 4.2123 (1.0); 3.8842(7.5); 3.8735 (13.0); 3.8634 (7.8); 3.3201 (103.8); 3.2938 (4.9); 3.2835(10.0); 3.2721 (9.7); 3.2610 (4.3); 32399 (1.3); 2.6748 (1.0); 2.6701(1.4); 2.6655 (1.0); 2.5055 (190.0); 2.5011 (244.6); 2.4967 (177.2);2.4494 (0.6); 2.3276 (1.4); 2.3242 (1.1); 2.2561 (0.6); 2.2356 (1.1);2.2230 (1.5); 2.2142 (1.6); 2.2015 (1.6); 2.1897 (1.2); 2.1810 (0.7);2.0889 (0.9); 2.0734 (1.5); 2.0661 (1.7); 2.0509 (1.3); 2.0397 (1.2);2.0325 (1.2); 1.9882 (0.6); 1.2982 (0 4); 1.2589 (0.5); 1.2354 (1.3);0.1459 (0.4); 0.0078 (3.5); −0.0002 (86.5); −0.0082 (3.6); −0.1499 (0.4)547 1.81 547: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.9803 (2.7); 8.9596(2.7); 8.4533 (1.8); 8.4383 (2.0); 8.4292 (2.0); 8.4129 (11.0); 7.9213(1.6); 7.9079 (1.6); 7.5407 (2.0); 7.5240 (2.5); 7.5175 (4.0), 7.4943(2.0); 7.3844 (5.7); 7.3618 (5.8); 7.3439 (4, 5); 7.3054 (2.7); 7.2871(2.9); 7.1782 (1.3); 7.1748 (1.4); 7.1612 (3.1); 7.1396 (1.7); 7.1361(1.6); 6.9171 (2.0); 6.8987 (3.4); 6.8820 (1.6); 6.8798 (1.6); 6.7965(3.8); 6.7760 (3.5), 5.7553 (11.4); 5.2518 (0.8); 5.2370 (1.7), 5.2169(1.7); 5.2030 (0.8); 4.2627 (2.9); 4.2496 (5.0); 4.2364 (2.9); 4.0557(1.2), 4.0379 (3.6); 4.0201 (3.7); 4.0023 (12); 3.3210 (22.0), 3.0647(10.6); 3.0522 (10.4); 2.6745 (0.4); 2.6702 (0.5); 2.6655 (0.4); 25056(68.9); 2.5012 (88.8); 2.4968 (63.5); 23277 (0.6),2 1932 (0.4); 2.1801(0.9); 2.1656 (0.9); 2.1595 (0.8); 2.1448 (1.4); 2.1311 (1.3); 2.1176(0.5); 2.0530 (0.5); 2.0414 (1.2); 2.0266 (1.4); 2.0130 (0.8); 2.0054(1.0); 1.9884 (16.0); 1.3975 (2.5); 1.1926 (4.0); 1.1748 (8.0); 1.1570(3.9); 0 0078 (1.4); −0.0002 (35.4); −0.0085 (1.2) 548 3.33 548: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.1827 (2.9); 9.1746 (2.9); 9.1624 (3.2);9.1541 (2.8); 8.6506 (10.0); 8.6441 (9.3); 8.3965 (3.4); 8.3810 (3.7);8.3731 (3.8); 8.3574 (3.6); 8.3157 (0.3); 7.7100 (3.6); 7.6872 (6.5);7.6643 (3.3); 7.5745 (1.2); 7.5534 (2.7); 7.5321 (2.9); 7.5111 (1.3);7.3747 (4.9); 7.3560 (6.6); 7.3355 (3.1); 7.3257 (2.3); 7.3156 (1.9);7.3046 (1.1); 7.2896 (1.7); 7.2743 (2.2); 7.2492 (2.1); 7.2300 (1.0);7.1862 (2.3); 7.1655 (4.9); 7.1478 (3.0); 6.9332 (3.2); 6.9148 (5.4);6.8959 (2.6); 6.8004 (6.6); 6.7799 (6.0); 5.7565 (3.2); 5.2752 (0.8);5.2508 (2.6); 5.2420 (2.6); 4.3002 (1.2); 4.2936 (1.0); 4.2819 (2.8);4.2723 (2.7); 4.2654 (3.1); 4.2555 (3.7); 4.2280 (2.8); 4.2046 (1.0);3.8768 (16.0); 3.3206 (24.3); 3.2960 (10.6); 3.2914 (10.6); 3.2511(1.4); 2.6702 (1.3); 2.5058 (182.0); 2.5015 (222.3); 2.4972 (161.2);2.3286 (1.3); 2.2435 (1.1); 2.2317 (1.3); 2.2215 (1.8); 2.2084 (1.8);2.1980 (1.8); 2.0647 (2.1); 2.0577 (1.9); 2.0466 (1.7); 2.0297 (1.5);1.9886 (0.8); 1.3976 (0.6); 1.2331 (0.4); 1.1748 (0.4); 0.1462 (0.3);−0.0002 (64.9) 549 3.59 549: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1861(3.0); 9.1775 (3.0); 9.1663 (3.2); 9.1573 (2.8); 8.6558 (10.4); 8.6485(9.7); 8.4036 (3.6); 8.3879 (4.0); 8.3801 (4.1); 8.3645 (3.7); 7.71581(3.7); 7.6930 (6.8); 7.6701 (3.6); 7.4984 (0.6); 7.4765 (1.7); 7.4585(2.0); 7.4508 (1.9); 7.4253 (0.8); 7.3779 (5.5); 7.3587 (6.9); 7.3388(2.2); 7.3334 (2.2); 7.3157 (1.4); 7.2930 (0.5); 7.1848 (2.4); 7.1676(5.0); 7.1497 (3.0); 6.9361 (3.1); 6.9174 (5.4); 6.8989 (2.5); 6.8016(6.9); 6.7814 (6.3); 5.7559 (2.5); 5.2740 (0.8); 5.2602 (2.1); 5.2512(2.6); 5.2405 (2.6); 5.2313 (2.0); 4.3086 (0.8); 4.3013 (1.2); 4.2948(1.0); 4.2818 (2.8); 4.2730 (2.7); 4.2658 1 (3.2); 4.2565 (3.6); 4.2288(2.8); 4.2034 (1.0); 3.8760 (16.0); 3.3215 (55.4); 3.2905 (11.0); 3.2507(1.4); 2.6706 (0.9); 2.5058 (119.4); 2.5015 (151.2); 2.4972 (110.3);2.3287 (0.9); 2.3246 (0.7); 2.2345 (1.2); 2.2183 (1.8); 2.2090 (1.8);2.2017 (1.8); 2.0818 (1.2); 2.0746 (1.7); 2.0663 (2.0); 2.0592 (1.9);2.0404 (1.5); 2.0321 (1.5); 2.0254 (1.2); 1.2343 (0.6); −0.0002 (41.6)550 3.94 550: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.2014 (2.6); 9.1811(2.6); 8.7076 (8.9); 8.4095 (1.7); 8.3941 (1.9); 8.3860 (1.9); 8.3705(1.8); 7.7354 (16.0); 7.7206 (2.0); 7.6972 (3.6); 7.674 0 (1.8); 7.3844(2.5); 7.3654 (2.7); 7.1898 (1.2); 7.1721 (2.6); 7.1543 (1.6); 6.9445(1.7); 6.9254 (3.0); 6.9075 (1.5); 6.8061 (3.4); 6.7859 (3.1); 5.7556(5.5); 5.2691 (0.7); 5.2558 (1.6); 5.2362 (1.6); 5.2219 (0.7); 4.3031(0.6); 4.2966 (0.6); 4.2847 (1.4); 4.2684 (1.7); 4.2592 (2.1); 4.2512(1.6); 4.2303 (1.6); 4.2087 (0.6); 4.2024 (0.5); 3.8768 (8.7); 3.3202(36.4); 3.2865 (6.7); 3.2752 (6.4); 3.2441 (0.8); 2.6703 (0.7); 2.5053(96.3); 2.5013 (1 18.5); 2.4974 (89.0); 2.3275 (0.6); 2.2343 (0.7);2.2204 (1.0); 2.2115 (1.1); 2.1996 (1.1); 2.1886 (0.8); 2.0703 (1.2);2.0576 (0.9); 2.0431 (0.8); 2.0347 (0.7); 1.3974 (0.4); 1.2345 (0.4);−0.0002 (27.3) 553 4.18 553: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1942(4.5); 9.1740 (4.6); 8.6557 (16.0); 8.3213 (6.5); 8.2983 (7.3); 8.2397(0.6); 7.8522 (0.4); 7.8288 (0.5); 7.8164 (7.8); 7.7936 (7.3); 7.6328(14.6); 7.5168 (0.4); 7.3705 (4.3); 7.3519 (4.8); 7.1870 (2.2); 7.1668(4.5); 7.1485 (2.8); 6.9330 (3.1); 6.9143 (5.5); 6.8959 (2.6); 6.8001(6.2); 6.7796 (5.6); 5.2596 (1.3); 52452 (2.9); 5.2264 (2.8); 5.2114(1.2); 4.2957 (1.1); 4.2877 (1.0); 4.2761 (2.5); 4.2673 (2.4); 4.2605(2.8); 4.2489 (3.1); 4.2407 (2.7); 4.2265 (2.3); 4.2194 (2.9); 4.1983(1.1); 4.0552 (0.9); 4.0376 (2.5); 4.0198 (2.5); 4.0023 (0.8); 3.8740(14.9); 3.3214 (154.1); 3.2935 (5.8); 3.2822 (11.0); 3.2705 (10.5);3.2585 (4.9); 3.2385 (1.7); 3.2278 (1.0); 2.6701 (1.4); 2.5048 (207.4);2.5012 (254.2); 2.3283 (1.5); 2.2354 (1.0); 2.2257 (1.3); 2.2134 (1.8);2.2038 (1.8); 21918 (1.9); 2.1798 (1.4); 2.0681 (1.3); 2.0602 (1.8);2.0537 (2.0); 2.0381 (1.6); 2.0268 (1.4); 2.019 4 (1.3); 1.9883 (10.2);1.3975 (3.1); 1.1926 (2.6); 1.1748 (5.2); 1.1569 (2.6); −0.0002 (37.7)556 3.76 556: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1775 (4.0); 9.1574(4.0); 8.6286 (16.0); 8.2793 (6.4); 8.2565 (7.2); 7.7842 (7.7); 7.7614(7.2); 7.3674 (3.9); 7.3493 (4.2); 7.3373 (1.2); 7.331 (1.8); 7.3260(1.1); 7.3134 (2.1); 7.3077 (3.5); 7.3022 (2.0); 7.2894 (12); 7.2839(1.8); 7.2783 (1.0); 7.1848 (19); 7.1813 (1.9); 7.1639 (4.0); 7.1462(2.5); 7.1426 (2.4); 7.0495 (3.6); 7.0319 (3.7); 6.9289 (2.8); 6.9112(4.9); 6.8933 (2.3); 6.7977 (5.5); 6.7777 (5.0); 5.2649 (1.1); 5.2506(2.5); 5.2315 (2.4); 5.2174 (1.1); 4.3044 (0.7); 4.2959 (0.9); 4.2888(0.8); 4.2769 (2.2); 4.2680 (2.1); 4.2605 (2.5); 4.2509 (3.0); 4.2426(2.4); 4.2290 (2.0); 4.2219 (2.6); 4.2011 (0.9); 4.1935 (0.7); 4.0555(0.5); 4.0377 (1.3); 4.0200 (13); 4.0024 (0.4); 3.9436 (0.5); 3.9000(10); 3.8818 (7.6); 3.8708 (13.2); 3.8600 (7.7); 3.8413 (0.9); 3.3245(50.8); 3.2916 (4.7); 3.2805 (9.6); 3.2687 (9.2); 3.2568 (4.1); 3.2378(1.4); 3.2256 (0.8); 2.6700 (0.7); 2.5055 (102.0); 2.5013 (130.9);2.4971 (94.4); 2.3278 (0.7); 2.3235 (0.6); 2.2484 (0.5); 2.2360 (0.8);2.2276 (1.1); 2.2147 (1.6); 2.2056 (1.6); 2.1931 (1.6); 2.1805 (1.1);2.1718 (0.7); 2.0755 (0.8); 2.0686 (1.1); 2.0602 (1.5); 2.0533 (1.7);2.0417 (1.3); 2.0374 (1.3); 20257 (1.2); 20184 (1.1); 2.0112 (0.7);2.0030 (0.5); 1.9883 (5.2); 1.3974 (2.9); 1.1927 (1.3); 1.1749 (2.7);1.1570 (1.3); 0.0076 (2.5); −0.0002 (60.6); −0.0083 (2.4) 557 4.23 557:¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1770 (4.0); 9.1568 (4.0); 8.6318(16.0); 8.2815 (6.3); 8.2586 (7.2); 7.7872 (7.7); 7.7643 (7.2); 7.5227(2.3); 7.5178 (3.8); 7.5126 (2.4); 7.500 6 (2.4); 7.4956 (3.8); 7.4903(2.2); 7.3684 (3.9); 7.3501 (4.2); 7.2192 (3.2); 7.1851 (3.5); 7.1820(3.5); 7.1648 (4.7); 7.1470 (2.6); 6.9298 (2.8); 6.9121 (4.8); 6.8925(2.2); 6.7984 (5.5); 6.7782 (5.0); 5.2636 (1.1); 5.2493 (2.5); 5.2297(2.4); 5.2151 (1.1); 4.3038 (0.7); 4.2952 (0.9); 4.2888 (0.8); 4.2770(2.2); 4.2672 (2.1); 4.2608 (2.5); 4.2508 (3.0); 4.2422 (2.3); 4.2287(1.9); 4.2214 (2.5); 4.2007 (0.9); 4.1935 (0.7); 4.0556 (0.6); 4.0380(1.7); 4.0202 (1.7); 4.0025 (0.6); 3.8712 (12.8); 3.8615 (7.6); 3.8422(1.0); 3.3270 (205.6); 3.2914 (4.9); 3.2806 (9.1); 3.2689 (8.6); 3.2572(4.0); 3.2371 (1.4); 3.2266 (0.9); 2.6709 (1.1); 2.5062 (163.1); 2.5020(209.0); 2.4978 (151.9); 2.3325 (0.9); 2.3283 (1.2); 2.2365 (0.8);2.2271 (1.2); 2.2144 (1.6); 2.2047 (1.6); 2.1929 (1.6); 2.1816 (1.1);2.0760 (0.8); 2.0596 (1.5); 2.0530 (1.7); 2.0413 (1.3); 2.0256 (1.2);2.0181 (1.1); 1.9885 (7.1); 1.3976 (3.1); 1.1928 (1.8); 1.1750 (3.6);1.1571 (1.8); −0.0001 (4.8) 558 4.13 558: ¹H-NMR (400.0 MHz, d₆-DMSO): δ= 9.1706 (2.1); 9.1527 (2.1); 8.6027 (16.0); 8.3154 (0.4); 8.2902 (6.2);8.2673 (7.0); 7.8025 (8.8); 7.7881 (4.9); 7.7796 (7.8); 7.7481 (1.9);7.728 6 (3.3); 7.7088 (1.6); 7.6194 (3.7); 7.3615 (3.8); 7.3434 (4.1);7.1811 (1.8); 7.1774 (1.8); 7.1595 (3.9); 7.1424 (2.4); 6.9232 (2.7);6.9052 (4.6); 6.8870 (2.1); 6.7953 (5.5); 6.7750 (4.9); 5.7551 (2.1);5.2581 (1.1); 5.2446 (2.4); 5.2255 (2.4); 5.2107 (1.0); 4.2995 (0.7);4.2915 (0.9); 4.2856 (0.9); 4.2727 (2.2); 4.2642 (2.1); 4.2566 (2.4);4.2466 (2.5); 4.2376 (2.0); 4.2163 (2.1); 4.1951 (0.8); 4.0377 (0.4);4.0201 (0.4); 3.8775 (11.0); 3.3239 (26 3.3); 3.2894 (6.2); 2.6705(1.7); 2.5236 (4.5); 2.5060 (239.6); 2.5017 (306.1); 2.4975 (218.6); 23284 (1.8); 2.2452 (0.5); 2.2233 (1.1); 2.2104 (1.6); 2.2010 (1.6);2.1894 (1.6); 2.1774 (1.2); 2.0573 (1.4); 2.0498 (1.6); 2.0372 (1.3);2.0225 (1.1); 1.9886 (1.7); 1.3974 (1.0); 1.1924 (0.4); 1.1748 (0.9);1.1577 (0.4); 0.1461 (0.6); 0.0077 (5.0); −0.0002 (134.8); −0.0084(5.2); −0.1496 (0.6) 564 564: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1810(3.4); 9.1696 (3.5); 9.1614 (3.8); 9.1496 (3.2); 8.6214 (12.6); 8.6138(11.8); 8.3155 (9.4); 8.2926 (10.6); 7.8206 (10.0); 7.7978 (9.3); 7.7086(2.5); 7.6910 (5.4); 7.6854 (4.8); 7.6715 (3.4); 7.6673 (2.9); 7.3843(1.6); 7.3653 (9.7); 7.3517 (10.5); 7.3473 (13.2); 7.3334 (5.8); 7.3249(2.6); 7.3201 (3.2); 7.3053 (2.8); 7.2898 (1.2); 7.1810 (2.8); 7.1612(6.0); 7.1427 (3.7); 6.9258 (3.4); 09073 (5.7); 6.8889 (2.7); 6.7951(8.5); 0.7751 (7.6); 5.2617 (1.1); 5.2413 (3.1); 5.2284 (3.2); 4.3001(1.0); 4.2943 (1.4); 4.2870 (1.2); 4.2748 (3.3); 4.2656 (3.1); 4.2585(3.6); 4.2497 (3.8); 4.2408 (3.2); 4.2317 (2.4); 4.2203 (3.4); 4.2129(2.7); 4.1923 (1.3); 3.8727 (16.0); 3.3218 (136.5); 3.3010 (10.8);3.2915 (10.8); 3.2796 (9.0); 3.2589 (3.1); 3.2398 (1.7); 2.6700 (2.2);2.5051 (310.4); 2 5010 (398.1); 2.4968 (287.4); 2.4242 (0.4); 2.3275(2.3); 22091 (2.0); 2.2014 (2.2); 2.1944 (2.1); 2.1809 (1.7); 2.0525(22); 2.0436 (2.2); 2.0258 (1.9); 2.0176 (1.6); 1.2348 (0.8); −0.0003(13.2) 565 4.03 565:¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1794 (1.1);9.1588 (1.1); 8.7822 (0.5); 8.6253 (3.8); 8.6202 (3.9); 8.3083 (2.6);8.2853 (2.9); 7.8100 (3.2); 7.7871 (3.1); 7.5936 (0.8); 7.5864 (0.9);7.5823 (0.9); 7.5752 (0.9); 7.5711 (1.0); 7.5643 (1.2); 7.5604 (1.0);7.5534 (0.9); 7.4579 (0.8); 7.4511 (0.8); 7.4423 (0.8); 7.4357 (0.8);7.4271 (1.0); 7.4220 (1.0); 7.4150 (1.0); 7.4053 (2.2); 7.4002 (1.1);7.3875 (1.7); 7.3829 (0.9); 7.3655 (2.0); 7.3489 (1.5); 7.1836 (0.8);7.1634 (1.6); 7.1453 (1.0); 6.9293 (1.1); 6.9265 (1.2); 6.9101 (1.8);6.8921 (0.9); 6.8893 (0.9); 6.7963 (2.2); 6.7760 (1.8); 5.2433 (0.8);5.2305 (0.7); 4.2945 (0.4); 4.2750 (0.9); 4.2602 (0.9); 4.2468 (0.9);4.2383 (0.9); 4.2248 (0.8); 4.2184 (1.0); 4.1975 (0.4); 3.8814 (3.0);3.8723 (5.0); 3.8602 (3.1); 3.8410 (0.5); 3.3215 (139 8); 3.2898 (3.6);3.2785 (3.4); 2.6746 (1.3); 2.6702 (1.7); 2.6655 (1.2); 2.5235 (4.2);2.5187 (6.8); 2.5100 (110.3); 2.5057 (227.6); 2.5012 (299.7); 2.4966(210.2); 2.4922 (97.2); 2.3368 (0.6); 2.3323 (1.2); 2.3278 (1.7); 2.3233(1.2); 2.2084 (0.6); 2.1892 (0.6); 2.0604 (0.5); 2.0532 (0.7); 2.0449(0.6); 2.0371 (0.5); 2.0276 (0.4); 2.0192 (0.5); 1.5301 (3.1); 1.4948(3.2); 1.4885 (1.2); 1.4529 (0.9); 1.3976 (16.0); 1.2344 (0.4); −0.0002(8.6) 566 1.71 566: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.9879 (3.8);8.9680 (3.8); 8.4481 (5.6); 8.4300 (12.0); 8.4220 (8.5); 7.9521 (0.3);7.9237 (2.0); 7.8814 (15.0); 7.8752 (16.0); 7.8612 (2.1); 7.6249 (5.2);7.6083 (8.1); 7.5614 (6.4); 7.5405 (6.8); 7.5226 (4.2); 7.4339 (4.4);7.4279 (4.8); 7.4173 (4.7); 7.4114 (4.0); 7.3027 (4.2); 7.2830 (4.5);7.1708 (2.8); 7.1673 (2.8); 7.1501 (5.7); 7.1322 (3.5); 7.1285 (3.3);6.9055 (4.0); 6.9032 (42); 6.8847 (7.0); 6.8684 (3.2); 6.8659 (3.2);6.7898 (7.8); 6.7694 (7.1); 5.7569 (11.9); 5.2623 (1.4); 5.2467 (3.2);5.2284 (3.1); 5.2128 (1.3); 4.9059 (4.0); 4.8931 (8.8); 4.8804 (4.0);4.2857 (0.9); 4.2659 (3.8); 42579 (5.8); 4.2484 (6.9); 4.2336 (4.0);42151 (1.0); 4.0556 (0.4); 4.0378 (1.2); 4.0198 (1.1); 4.0021 (0.4);3.6850 (2.4); 3.6707 (7.8); 3.6573 (10.0); 3.6444 (4.9); 3.5952 (5.7);3.5840 (6.8); 3.5721 (4.3); 3.3213 (90.6); 2.6744 (1.3); 2.6702 (1.8);2.6657 (1.3); 2.5234 (4.8); 2.5098 (122.4); 2.5055 (249.9); 2.5011(329.4); 2.4966 (234.1); 2.4923 (111.1); 2.3323 (1.3); 2.3278 (1.9);2.3234 (1.4); 2.1873 (0.7); 2.1740 (1.2); 2.1642 (1.4); 2.1534 (1.8);2.1403 (2.5); 2.1243 (2.1); 2.1117 (1.0); 2.0664 (1.0); 2.0521 (2.3);2.0411 (2.4); 2.0253 (1.7); 2.0167 (1.6); 2.0074 (1.3); 1.9886 (5.2);1.2582 (0.4); 1.2344 (1.0); 1.1922 (1.2); 1.1743 (2.6); 1.1567 (1.2);0.1459 (0.7); 0.0079 (5.6); −0.0002 (166.0); −0.0084 (5.9); −0.1494(0.7) 567 1.42 567: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0073 (3.6);8.9868 (3.7); 8.4799 (13.7); 8.4638 (3.9); 8.4434 (4.0); 7.9315 (1.6);7.9195 (3.1); 7.9073 (1.7); 7.7132 (4.1); 7.6963 (5.2); 7.5965 (0.8);7.5887 (1.0); 7.5790 (4.5); 7.5685 (2.0); 7.5606 (5.4); 7.5581 (5.4);7.5477 (1.9); 7.5399 (3.8); 7.5256 (0.8); 7.3116 (3.6); 7.2930 (4.0);7.1762 (3.3); 7.1726 (3.6); 7.1555 (5.2); 7.1378 (2.3); 7.1341 (2.2);6.9102 (2.7); 6.8919 (4.6); 6.8733 (2.2); 6.7949 (5.1); 6.7747 (4.7);5.7571 (3.2); 5.2731 (1.0); 5.2573 (2.3); 5.2384 (2.3); 5.2240 (1.0);4.9044 (2.7); 4.8916 (6.1); 4.8787 (2.9); 4.3020 (0.4); 4.2928 (0.6);4.2733 (2.5); 4.2651 (3.9); 4.2551 (4.4); 4.2492 (4.0); 4.2396 (2.5);4.2218 (0.6); 3.6817 (1.5); 3.6675 (5.2); 3.6542 (6.9); 3.6416 (3.4);3.6086 (3.1); 3.5963 (6.2); 3.5830 (4.7); 3.5689 (1.4); 3.3218 (25.0);2.6745 (0.7); 2.6703 (1.0); 2.6662 (0.8); 2.5233 (2.6); 2.5055 (133.6);2.5012 (174.2); 2.4970 (126.3); 2.3276 (1.0); 2.1948 (0.4); 2.1840(0.8); 2.1720 (0.9); 2.1606 (1.2); 2.1486 (1.7); 2.1341 (1.4); 2.1194(0.7); 2.0856 (16.0); 2.0641 (1.7); 2.0532 (1.6); 2.0376 (1.2); 2.0288(1.1); 2.0193 (0.9); 2.0128 (0.7); 2.0046 (0.4); 1.9887 (0.9); 1.2351(0.7); 1.1745 (0.4); −0.0001 (3.6) 568 1.53 568: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 9.0342 (1.9); 9.0140 (2.0); 8.5727 (6.2); 8.4892 (2.2);8.4672 (2.2); 8.4420 (0.6); 8.2975 (0.4); 8.2615 (1.1); 8.0721 (0.9);8.0606 (1.6); 8.0483 (1.0); 7.9562 (0.5); 7.8662 (2.1); 7.8497 (2.5);7.8153 (16.0); 7.7977 (0.8); 7.5936 (1.8); 7.5727 (2.1); 7.5543 (1.6);7.3204 (1.8); 7.3024 (2.2); 7.1821 (0.9); 7.1645 (2.0); 7.1470 (1.4);7.1436 (1.4); 6.9222 (1.3); 6.9040 (2.4); 6.8850 (1.3); 6.8045 (2.6);6.7848 (2.5); 5.7572 (7.2); 5.7396 (0.3); 5.2804 (0.6); 5.2654 (1.3);5.2464 (1.4); 5.2318 (0.7); 4.9134 (1.6); 4.9007 (3.2); 4.8881 (1.6);4.3032 (0.4); 4.2833 (1.4); 4.2743 (2.1); 4.2633 (2.5); 1.2580 (2.6);4.2482 (1.7); 4.2305 (0.6); 4.0379 (0.8); 4.0201 (0.9); 4.0023 (0.3);3.6661 (2.9); 3.6533 (3.7); 3.6407 (2.2); 3.6145 (2); 3.6024 (3.4);3.5894 (2.6); 3.3241 (7.3); 3.3074 (0.5); 2 5060 (41.9); 2.5018 (53.4);2.4975 (40.1); 2.1877 (0.4); 2.1793 (0.5); 2.1681 (0.8); 2.1557 (1.0);2.1410 (0.9); 2.1258 (0.6); 2.0946 (0.5); 2.0799 (0.9); 2.0699 (1.0);2.0542 (0.8); 2.0447 (0.7); 2.0357 (0.6); 2.0293 (0.5); 1.9890 (3.5);1.2988 (0.4); 1 2585 (0.5); 1.2312 (0.7); 1.1925 (1.0); 1.1747 (1.8);1.1569 (1.0); −0.0002 (1.2) 576 3.90 576: ¹H-NMR (400.0 MHz, d₆-DMSO): δ= 20.0029 (0.9); 9.1889 (6.0); 9.1694 (6.2); 8.6464 (14.7); 8.6381(15.0); 8.3318 (10.9); 8.3089 (11.9); 7.8301 (11.0); 7.8072 (10.0);7.6892 (1.6); 7.6682 (2.6); 7.6486 (2.6); 7.4026 (1.1); 7.3714 (3.5);7.3527 (4.2); 7.1816 (5.1); 7.1646 (7.5); 7.1472 (4.8); 6.9296 (4.4);6.9103 (7.1); 6.8923 (3.8); 6.7973 (8.0); 6.7765 (7.6); 5.2293 (3.2);4.2951 (1.7); 4.2767 (3.3); 4.2608 (3.3); 4.2507 (3.5); 4.2420 (3.3);4.2203 (3.7); 4.1924 (1.5); 3.9161 (1.0); 3.9087 (1.1); 3.8728 (16.0);3.7425 (1.0); 3.3196 (381.7); 3.2976 (12.2); 3.2873 (11.7); 3.2380(1.9); 2.6744 (7.0); 2.6702 (9.7); 2.6655 (7.0); 2.6612 (3.6); 2.5233(22.0); 2.5099 (648.2); 2.5055 (1360.8); 2.5010 (1822.1); 2.4965(1299.0); 2.4920 (613.8); 2.4282 (2.0); 2.3323 (7.9); 2.3277 (10.7);2.3234 (7.8); 2.2851 (1.0); 2.2044 (2.7); 2.0556 (2.4); 2.0356 (2.2);1.2408 (1.1); −0.0002 (68.2) 577 1.66 577: ¹H-NMR (400.0 MHz, d₆-DMSO):δ = 8.9783 (4.8); 8.9578 (4.8); 8.5458 (3.4); 8.5302 (3.7); 8.5222(3.6); 8.5068 (3.4); 8.4827 (1.4); 8.4655 (0.4); 8.4574 (0.4); 8.4398(0.4); 8.4133 (2.7); 8.4054 (16.0); 8.0443 (0.8); 8.0308 (0.5); 8.0114(0.4); 7.9945 (1.9); 7.9831 (3.6); 7.9722 (1.9); 7.7219 (5.6); 7.7183(5.8); 7.7019 (6.8); 7.6982 (6.6); 7.5396 (0.4); 7.5281 (3.8); 7.5054(6.4); 7.4834 (4.5); 7.4711 (5.3); 7.4516 (9.8); 7.4431 (1.6); 7.4319(5.6); 7.4231 (0.9); 7.3921 (0.3); 7.3727 (0.6); 7.3473 (6.3); 7.3436(6.5); 7.3281 (5.6); 7.3245 (4.7); 7.3118 (0.8); 7.2873 (4.7); 7.2693(5.2); 7.1660 (2.4); 7.1634 (2.4); 7.1455 (5.1); 7.1282 (3.2); 7.1246(3.0); 6.8960 (3.8); 6.8769 (6.2); 6.8606 (2.8); 6.7853 (6.9); 6.7650(6.3); 6.6074 (0.5); 6.5916 (0.4); 5.7570 (8.6); 5.2502 (1.6); 5.2353(3.1); 5.2157 (3.0); 5.2010 (1.4); 4.9112 (3.8); 4.8980 (8.6); 4.8853(3.9); 4.2747 (0.8); 4.2402 (7.3); 4.2276 (4.6); 4.2100 (0.7); 4.1986(0.4); 4.0553 (0.7); 4.0376 (2.0); 4.0197 (1.9); 4.0019 (0.8); 3.6838(2.3); 3.6695 (7.4); 3.6560 (9.4); 3.6437 (4.5); 3.5967 (4.6); 3.5846(8.3); 3.5711 (6.6); 3.5569 (2.0); 3.5289 (0.4); 3.4240 (0.3); 3.3211(225.0); 2.6744 (2.4); 2.6700 (32); 2.6655 (2.3); 2.6025 (0.4); 2.5795(0.3); 2.5234 (7.9); 2.5096 (213.1); 2.5055 (434.5); 2.5010 (573.6);2.4966 (408.4); 2.4923 (193.6); 2.4434 (0.9); 2.4385 (0.9); 2.3322(2.3); 2.3277 (3.3); 2.3232 (2.3); 2.1689 (1.4); 2.1475 (1.8); 2.1338(2.6); 2.1207 (2.2); 2.1056 (1.0); 2.0549 (1.1); 2.0409 (2.3); 2.0263(2.3); 2.0117 (1.7); 2.0043 (1.6); 1.9886 (9.4); 1.9081 (0.3); 1.3974(0.7); 1.3508 (0.3); 1.2979 (2.2); 1.2583 (3.0); 1.2351 (2.6); 1.1922(2.3); 1.1743 (4.8); 1.1565 (2.2); 0.8663 (0.4); 0.8537 (0.6); 0.8378(0.4); −0.0002 (22.2) 578 1.84 578: ¹H-NMR (400.0 MHz, d₆-DMSO): δ =8.9985 (2.2); 8.9780 (2.3); 8.5049 (8.6); 8.4947 (2.0); 8.4861 (1.8);8.4710 (1.5); 8.1238 (1.0); 8.1117 (1.8); 8.1003 (1.0); 7.6592 (3.0);7.6544 (5.7); 7.6497 (3.2); 7.5218 (1.8); 7.4987 (3.4); 7.4750 (10.7);7.4705 (9.2); 7.2997 (2.3); 7.2817 (2.5); 7.1770 (1.1); 7.1734 (1.1);7.1561 (2.4); 7.1 383 (1.5); 7.1350 (1.4); 6.9084 (1.7); 6.8916 (3.0);6.8733 (1.4); 6.8711 (1.4); 6.7964 (3.3); 6.7761 (3.0); 5.7570 (13.6);5.2638 (0.6); 5.2483 (1.5); 5.2298 (1.5); 5.2142 (0.7); 4.9160 (1.7);4.9034 (4.0); 4.8907 (1.9); 4.2892 (0.4); 4.2697 (1.7); 4.2614 (2.4);4.2520 (3.0); 4.2376 (1.8); 4.2191 (0.4); 4.0557 (0.6); 4.0379 (1.9);4.0201 (1.9); 4.0023 (0.6); 3.6763 (1.0); 3.6615 (3.2); 3.6485 (4.3);3.6362 (2.3); 3.6094 (2.1); 3.5974 (3.8); 3.5842 (2.9); 3.5725 (0.9);3.3230 (35.7); 2.6747 (0.4); 2.6706 (0.5); 2.6663 (0.4); 2.5238 (1.2);2.5059 (68.9); 2.5015 (90.7); 2.4971 (65.0); 2.3284 (0.5); 2.3240 (0.4);2.1790 (0.5); 2.1660 (0.6); 2.1552 (0.8); 2.1422 (1.1); 2.1265 (0.9);2.1138 (0.4); 2.0744 (0.4); 2.0596 (1.1); 2.0484 (1.0); 2.0333 (0.7);2.0239 (0.7); 2.0148 (0.6); 2.0076 (0.4); 1.9971 (0.3); 1.9888 (8.2);1.3971 (16.0); 1.2586 (0.4); 1.1925 (2.1); 1.1747 (4.2); 1.1568 (2.0);−0.0002 (3.7) 579 1.61 579: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0615(0.4); 9.0402 (0.5); 9.0006 (7.4); 8.9800 (7.6); 8.6025 (1.7); 8.5834(5.4); 8.5682 (5.9); 8.5596 (5.8); 8.5445 (5.4); 8.5056 (1.2); 8.4832(15.4); 8.4772 (16.0); 8.4524 (0.5); 8.4436 (0.4); 8.4293 (0.3); 8.1268(3.0); 8.1146 (2.0); 8.0994 (2.0); 8.0864 (3.4); 7.6673 (1.6); 7.6596(2.1); 7.6507 (2.3); 7.6445 (3.2); 7.6391 (3.2); 7.6309 (3.2); 7.6236(3.1); 7.6180 (3.2); 7.6113 (2.0); 7.6033 (1.7); 7.5953 (1.4); 7.5580(5.5); 7.5351 (10.2); 7.5124 (5.4); 7.4985 (1.0); 7.4754 (1.7); 7.3275(0.5); 7.3007 (7.9); 7.2816 (8.6); 7.2356 (2.1); 7.2214 (3.4); 7.2145(3.9); 7.1940 (2.2); 7.1750 (4.5); 7.1713 (4.3); 7.1539 (8.4); 7.1364(5.3); 7.1328 (4.8); 6.9344 (0.4); 6.9060 (6.0); 6.8874 (10.0); 6.8689(5.0); 6.8113 (0.6); 6.7940 (12.0); 6.7918 (11.6); 6.7736 (10.7); 6.7713(9.7); 5.7574 (15.4); 5.2606 (2.2); 5.2456 (4.9); 5.2266 (4.8); 5.2116(2.0); 4.9170 (4.8); 4.9062 (9.9); 4.9041 (10.1); 4.8926 (5.4); 4.8800(0.5); 4.2823 (1.2); 4.2589 (7.8); 4.2481 (10.8); 4.2360 (6.9); 4.2174(1.2); 4.2072 (0.5); 4.0559 (0.9); 4.0380 (2.7); 4.0203 (2.8); 4.0024(0.9); 3.6805 (3.2); 3.6666 (11.4); 3.6537 (15.0); 3.6414 (8.3); 3.6174(42); 3.6062 (8.8); 3.5961 (10.2); 3.5835 (7.1); 3.5594 (1.0); 3.5452(0.4); 3.3229 (55.3); 2.6798 (0.6); 2.6752 (1.2); 2.6707 (1.6); 2.6660(1.2); 2.5240 (4.0); 2.5191 (6.4); 2.5106 (102.4); 2.5061 (214.3);2.5016 (285.4); 2.4971 (201.0); 2.4926 (93.2); 2.3326 (1.1); 2.3283(1.6); 2.3239 (1.2); 2.1891 (1.0); 2.1779 (2.0); 2.1654 (2.1); 2.1559(2.6); 2.1423 (4.1); 2.1277 (3.3); 2.1137 (1.4); 2.0676 (1.7); 2.0536(3.7); 2.0411 (3.4); 2.0261 (2.4); 2.0174 (2.4); 2.0082 (1.9); 1.9890(12.6); 1.3971 (1.9); 1.2992 (2.0); 1.2588 (2.8); 1.2348 (1.5); 1.1924(3.3); 1.1747 (6.6); 1.1569 (3.2); 0.8537 (0.4); 0.0081 (0.4); −0.0002(12.9); −0.0081 (0.4) 589 2.43 589: ¹H-NMR (400.0 MHz, d₆-DMSO): δ =9.3204 (1.1); 9.3135 (1.1); 9.3003 (1.2); 9.2927 (1.0); 8.5653 (7.4);8.3124 (1.6); 8.3036 (1.4); 8.2966 (1.7); 8.2873 (1.7); 8.2791 (0.4);7.7025 (2.2); 7.6989 (2.4); 7.6825 (2.7); 7.6788 (2.7); 7.6719 (0.8);7.6538 (3.4); 7.6470 (3.3); 7.6381 (6.8); 7.4567 (0.8); 7.4467 (0.8);7.4374 (1.7); 7.4275 (1.6); 7.4178 (1.1); 7.4076 (1.0); 7.3623 (2.7);7.3323 (3.6); 7.3134 (0.9); 7.1863 (0.9); 7.1659 (2.0); 7.1482 (1.2);6.9252 (1.3); 6.9067 (2.2); 6.8881 (1.0); 6.8028 (2.7); 6.7823 (2.4);5.7568 (16.0); 5.2942 (0.5); 5.2792 (1.2); 5.2607 (1.2); 5.2464 (0.6);5.1484 (0.9); 5.1392 (1.6); 5.1338 (1.5); 5.1246 (0.8); 4.2956 (0.4);4.2771 (1.2); 4.2614 (2.0); 4.2522 (2.0); 4.2406 (1.0); 4.2328 (1.2);4.2129 (0.4); 4.2075 (0.3); 4.0374 (0.7); 4.0196 (0.6); 3.6661 (0.4);3.6505 (1.0); 3.6383 (1.8); 3.6256 (1.9); 3.5831 (0.4); 3.5455 (2.6);3.3210 (21.3); 3.3034 (0.4); 3.0572 (15.5); 2.6701 (0.6); 2.6654 (0.5);2.5051 (83.3); 2.5007 (109.1); 2.4964 (79.4); 2.3273 (0.6); 2.3233(0.5); 2.2266 (0.5); 2.2137 (0.8); 2.2033 (0.8); 2.1911 (0.8); 2.1798(0.6); 2.0667 (0.8); 2.0593 (0.9); 2.0497 (0.7); 2.0377 (0.6); 2.0327(0.6); 2.0238 (0.5); 1.9884 (2.9); 1.2347 (0.5); 1.1919 (0.8); 1.1742(1.5); 1.1564 (0.7); −0.0002 (9.7) 590 3.44 590: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 9.3230 (1.9); 9.3026 (1.9); 8.7282 (0.8); 8.6746 (0.3);8.5838 (8.2); 8.3304 (1.7); 8.3262 (1.8); 8.3102 (1.8); 8.3060 (2.0);7.9109 (4.6); 7.9048 (4.8); 7.6985 (1.1); 7.6845 (3.0); 7.6738 (3.3);7.6536 (2.8); 7.6410 (0.9); 7.6360 (1.4); 7.4926 (1.6); 7.4863 (1.7);7.4607 (1.5); 7.4549 (1.4); 7.3529 (1.9); 7.3362 (2.0); 7.1897 (1.2);7.1866 (1.2); 7.1682 (2.1); 7.1514 (1.3); 7.1473 (1.2); 6.9385 (0.3);6.9281 (1.4); 6.9100 (2.3); 6.8922 (1.1); 6.8203 (0.4); 6.8035 (2.9);6.7849 (2.4); 5.7568 (4.1); 5.2936 (0.6); 5.2778 (1.2); 5.2600 (1.2);5.2445 (0.6); 5.1331 (1.4); 4.3052 (0.4); 4.2974 (0.6); 4.2901 (0.6);4.2777 (1.3); 4.2616 (2.0); 4.2525 (2.0); 4.2406 (1.1); 4.2325 (1.2);4.2122 (0.4); 3.6684 (0.4); 3.6540 (0.9); 3.6401 (1.6); 3.6268 (1.8);3.5844 (0.4); 3.5555 (2.0); 3.5444 (2.6); 3.5068 (0.4); 3.4949 (0.4);3.3197 (31.2); 3.0560 (16.0); 3.0377 (1.8); 2.6746 (0.8); 2.6700 (1.1);2.6654 (0.8); 2.5231 (2.9); 2.5096 (69.2); 2.5054 (141.9); 2.5009(188.1); 2.4965 (135.6); 2.4922 (65.6); 2.3321 (0.8); 2.3276 (1.1);2.3232 (0.8); 2.2478 (0.4); 2.2268 (0.6); 2.2135 (0.9); 2.2041 (0.9);2.1919 (0.9); 2.1835 (0.6); 2.0762 (0.6); 2.0685 (0.8); 2.0611 (1.0);2.0519 (0.7); 2.0343 (0.7); 2.0262 (0.6); 1.9885 (0.4); 1.2580 (0.4);1.2349 (1.4); 0.0079 (0.4); −0.0002 (12.9) 591 3.25 591: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 9.3476 (1.8); 9.3272 (1.8); 8.7005 (7.3); 8.5245(0.4); 8.3686 (2.0); 8.3493 (2.2); 8.2720 (1.2); 7.9656 (0.5); 7.9319(2.0); 7.9142 (2.4); 7.8341 (16.0); 7.7034 (1.8); 7.6847 (2.0); 7.6642(1.4); 7.3800 (1.9); 7.3618 (2.0); 7.2027 (0.9); 7.1993 (0.9); 7.1815(2.0); 7.1641 (1.2); 7.1611 (1.2); 6.9518 (1.3); 6.9330 (2.3); 6.9146(1.2); 6.8173 (2.8); 6.7968 (2.5); 5.7572 (12.0); 5.3147 (0.5); 5.3002(1.2); 5.2813 (1.3); 5.2664 (0.6); 5.1438 (1.1); 5.1288 (2.4); 5.1136(1.1); 4.3120 (0.4); 4.3050 (0.4); 4.2928 (1.2); 4.2757 (1.9); 4.2668(1.9); 4.2535 (1.1); 4.2460 (1.3); 4.2258 (0.4); 4.2188 (0.4); 4.0382(0.9); 4.0204 (0.9); 3.6465 (1.0); 3.6331 (2.4); 3.6200 (2.6); 3.6066(1.4); 3.5492 (2.4); 3.5372 (2.9); 3.3260 (25.5); 3.3049 (0.4); 3.0624(14.0); 2.5058 (36.3); 2.5017 (45.5); 2.4977 (33.2); 2.2521 (0.4);2.2430 (0.5); 2.2305 (0.8); 2.2209 (0.8); 2.2089 (0.9); 2.1975 (0.7);2.1887 (0.4); 2.1046 (0.6); 2.0965 (0.8); 2.0895 (0.9); 2.0738 (0.7);2.0620 (0.6); 2.0537 (0.6); 1.9891 (3.8); 1.2320 (0.3); 1.1926 (1.0);1.1748 (1.9); 1.1572 (1.0); −0.0001 (4.5) 595 3.61 595: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 9.1408 (0.9); 9.1232 (1.7); 9.1128 (1.2); 9.1059(1.3); 8.5911 (7.4); 8.3494 (1.9); 8.3335 (2.1); 8.3258 (2.1); 8.3102(1.9); 8.1409 (0.4); 7.7554 (3.0); 7.7518 (3.1); 7.7353 (3.7); 7.7317(3.6); 7.6777 (2.3); 7.6551 (3.9); 7.6324 (2.2); 7.5002 (1.4); 7.4897(1.3); 7.4808 (2.9); 7.4702 (2.7); 7.4610 (1.8); 7.4505 (1.6); 7.4116(1.0); 7.4079 (1.1); 7.3993 (1.1); 7.3919 (1.8); 7.3883 (1.6); 7.3754(1.7); 7.3681 (12); 7.3560 (2.0); 7.3479 (1.6); 7.3377 (1.5); 7.3327(1.4); 7.1785 (1.3); 7.1608 (2.8); 7.1431 (1.7); 6.9110 (1.4); 6.8927(2.5); 6.8746 (1.2); 6.7951 (3.5); 6.7747 (3.2); 5.7569 (16.0); 5.2309(1.4); 5.2174 (1.3); 4.2882 (0.5); 4.2691 (1.6); 4.2537 (2.7); 4.2444(2.3); 4.2322 (1.3); 4.2033 (0.4); 4.0557 (0.6); 4.0378 (1.6); 4.0201(1.6); 4.0023 (0.6); 3.7509 (0.6); 3.7434 (0.5); 3.7279 (1.0); 3.7217(1.2); 3.7117 (0.7); 3.7041 (1.5); 3.6822 (1.2); 3.6640 (0.7); 3.6542(0.7); 3.6478 (1.1); 3.6339 (1.7); 3.6281 (1.2); 3.6209 (1.1); 3.6138(1.3); 3.6008 (1.6); 3.5817 (2.2); 3.5630 (1.8); 3.5434 (0.5); 3.3865(0.6); 3.3682 (1.5); 3.3552 (1.7); 3.3473 (2.1); 3.3228 (43.4); 3.2960(0.8); 3.2790 (0.6); 3.2636 (1.0); 3.2544 (1.1); 3.2470 (1.0); 3.2390(1.1); 3.2120 (1.6); 3.1913 (1.2); 3.1782 (1.4); 3.1674 (0.5); 3.1565(0.9); 3.1462 (0.7); 3.1236 (0.4); 3.0852 (14.4); 3.0806 (13.3); 2.6985(1.0); 2.6799 (1.2); 2.6746 (1.3); 2.6704 (1.5); 2.5233 (2.1); 2.5057(103.8); 2.5013 (135.2); 2.4969 (96.5); 2.3325 (0.6); 2.3281 (0.8);2.2037 (0.7); 2.1932 (0.9); 2.1822 (1.1); 2.1701 (1.0); 2.1617 (0.8);2.1490 (0.5); 2.0299 (1.2); 2.0158 (1.4); 1.9887 (8.2); 1.9661 (1.1);1.9539 (0.6); 1.4852 (0.6); 1.4798 (0.6); 1.4688 (1.0); 1.4532 (1.1);1.4363 (0.9); 1.4216 (0.6); 1.2352 (0.5); 1.1923 (1.8); 1.1745 (3.6);1.1567 (1.8); 0.0075 (0.3); −0.0002 (9.6) 596 2.30 596: ¹H-NMR (400.0MHz, d₆-DMSO): δ = 9.0701 (3.4); 9.0498 (3.5); 8.5625 (0.6); 8.5278(0.5); 8.4640 (2.2); 8.4489 (2.6); 8.4390 (11.6); 8.4253 (2.3); 8.1352(0.7); 7.8085 (0.8); 7.795 5 (1.7); 7.7758 (1.8); 7.7613 (0.9); 7.7046(6.4); 7.6992 (7.6); 7.6691 (0.7); 7.6622 (1.0); 7.6543 (0.9); 7.6470(1.4); 7.6418 (1.4); 7.6338 (1.4); 7.6213 (1.4); 7.6135 (0.9); 7.5969(2.8); 7.5738 (4.2); 7.5512 (2.2); 7.5380 (0.3); 7.4597 (6.8); 7.4558(6.8); 7.4405 (0.4); 7.2706 (2.3); 7.2503 (2.8); 7.2145 (1.7); 7.1920(0.9); 7.1737 (1.8); 7.1528 (3.5); 7.1353 (2.1); 6.8948 (1.7); 6.8760(2.8); 6.8579 (1.3); 6.7898 (4.9); 6.7697 (4.4); 6.2235 (4.2); 6.2186(7.2); 6.2137 (42); 6.1947 (0.4); 5.7572 (15.7); 5.2260 (1.1); 5.2118(2.2); 5.1921 (2.1); 5.1777 (0.9); 4.4811 (3.3); 4.4655 (7.5); 4.4500(3.9); 4.4309 (0.4); 4.2266 (4.2); 4.2215 (4.5); 4.0560 (1.1); 4.0380(3.4); 4.0202 (3.4); 4.0023 (1.2); 3.8362 (3.8); 3.8227 (3.4); 3.3218(25.8); 2.8900 (0.6); 2.7311 (0.6); 2.6707 (1.0); 2.5236 (2.6); 2.5057(130.4); 2.5014 (170.3); 2.4971 (122.6); 2.3282 (1.0); 2.1418 (0.9);2.1256 (1.2); 2.1084 (1.4); 2.0941 (1.3); 2.0746 (0.7); 2.0126 (1.0);1.9999 (1.6); 1.9888 (16.0); 1.9666 (1.0); 1.9535 (0.7); 1.2347 (0.6);1.1924 (3.8); 1.1746 (7.5); 1.1568 (3.7); 0.0080 (0.4); −0.0001 (12.0)597 1.84 597: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0160 (2.4); 8.9955(2.4); 8.5800 (1.6); 8.5647 (1.7); 8.5564 (1.7); 8.5410 (1.7); 8.5257(8.0); 8.2056 (1.8); 7.6979 (16.0); 7.5619 (1.8); 7.5385 (3.4); 7.5151(1.7); 7.2990 (2.3); 7.2808 (2.6); 7.1797 (1.1); 7.1764 (1.2); 7.1586(2.4); 7.1412 (1.5); 6.9103 (1.7); 6.8921 (2.9); 6.8735 (1.4); 6.7985(3.3); 6.7784 (3.0); 5.2605 (0.7); 5.2452 (1.5); 5.2258 (1.5); 5.2103(0.6); 4.9247 (1.7); 4.9122 (3.9); 4.8996 (1.8); 4.2873 (0.3); 4.2603(2.4); 4.2512 (3.2); 4.2197 (0.4); 3.6760 (0.9); 3.6623 (3.1); 3.6494(4.2); 3.6376 (2.3); 3.6131 (22); 3.6014 (3.8); 3.5884 (2.8); 3.3245(128.5); 2.6710 (0.9); 2.5058 (125.4); 2.5015 (161.2); 2.4973 (117.7);2.3284 (0.9); 2 1769 (0.5); 2.1553 (0.8); 2.1416 (1.1); 2.1263 (1.0);2.1128 (0.5); 2.0598 (1.1); 2.0478 (1.1); 2.0324 (0.8); 2.0239 (0.7);2.0143 (0.6); −0.0001 (5.0) 599 1.26 599: ¹H-NMR (400.0 MHz, d₆-DMSO): δ= 9.0562 (3.0); 9.0349 (3.1); 8.5743 (0.4); 8.4690 (1.5); 8.4526 (1.9);8.4440 (1.9); 8.4303 (1.6); 8.3837 (8.0); 8.1530 (1.3); 7.9531 (0.3);7.8091 (1.4); 7.7969 (1.3); 7.7809 (1.2); 7.7236 (3.8); 7.7207 (3.8);7.7033 (4.5); 7.6086 (1.1); 7.5735 (2.2); 7.5518 (3.6); 7.5294 (2.0);7.4708 (1.4); 7.4608 (1.8); 7.4511 (2.7); 7.4413 (3.2); 7.4317 (1.7);7.4217 (1.9); 7.3433 (2.1); 7.3279 (3.6); 7.3127 (2.0); 7.2532 (3.2);7.2358 (3.5); 7.2145 (0.4); 7.1976 (0.5); 7.1703 (2.3); 7.1507 (4.4);7.1322 (2.8); 6.9427 (0.3); 6.8980 (2.9); 6.8795 (4.7); 6.8617 (2.6);6.8121 (0.5); 6.7871 (4.7); 6.7668 (4.2); 5.7564 (16.0); 5.2306 (1.0);5.2157 (2.1); 5.1972 (2.0); 5.1830 (0.9); 4.3402 (3.3); 4.2258 (4.6);3.7613 (3.1); 3.5706 (0.3); 3.5591 (0.4); 3.5486 (0.4); 3.4758 (0.7);3.3304 (5.7); 3.1731 (0.6); 2.8900 (1.4); 2.7307 (1.4); 2.6707 (1.6);2.5587 (0.4); 2.5016 (305.4); 2.4478 (0.8); 2.4148 (0.4); 2.40 82 (0.4);2.3283 (1.8); 2.1700 (0.5); 2.1196 (1.4); 1.9881 (2.0); 1.9618 (1.2);1.1742 (0.4); −0.0003 (14.4) 606 2.63 606: ¹H-NMR (400.0 MHz, d₆-DMSO):δ = 20.0019 (0.4); 11.6374 (0.5); 9.3368 (2.0); 9.3164 (1.9); 8.6542(0.4); 8.6320 (8.0); 8.3582 (2.0); 8.3369 (2.2); 8.1752 (0.6); 8.1559(0.5); 7.7946 (2.0); 7.7787 (2.7); 7.7011 (2.2); 7.6792 (2.2); 7.6623(1.5); 7.6399 (0.6); 7.6304 (0.7); 7.6154 (0.9); 7.6105 (0.9); 7.5953(0.9); 7.5661 (0.6); 7.3732 (2.0); 7.3566 (2.2); 7.2327 (1.2); 7.2036(1.6); 7.1824 (2.2); 7.1642 (1.3); 6.9450 (1.6); 6.9252 (2.4); 6.9067(1.2); 6.8179 (2.7); 6.7965 (2.4); 5.3127 (0.7); 5.2980 (1.3); 5.2805(1.4); 5.2646 (0.6); 5.1508 (1.2); 5.1352 (2.6); 5.1201 (1.3); 4.3135(0.6); 1.3101 (0.6); 4.2925 (1.2); 4.2749 (1.8); 4.2657 (1.9); 4.2452(1.4); 4.2228 (0.6); 3.6428 (2.3); 3.6278 (2.6); 3.6139 (1.6); 3.5956(0.5); 3.5628 (2.5); 3.5489 (3.0); 3.3286 (367.5); 3.0681 (16.0); 2.6830(4.0); 2.6784 (5.4); 2.6738 (4.0); 2.6571 (0.4); 2.5916 (0.5); 2.5585(1.2); 2.5138 (734.5); 2.5095 (960.4); 2.5050 (690.4); 2.4327 (0.8);2.3888 (0.5); 2.3406 (4.0); 2.3362 (5.6); 2.3320 (4.1); 2.2638 (0.5);2.2521 (0.8); 2.2294 (0.9); 2.2202 (0.8); 2.2097 (0.9); 2.1954 (0.9);2.1014 (0.6); 2.0870 (1.1); 2.0807 (1.0); 2.0641 (0.9); 2.0539 (0.8);1.7536 (0.4); 0.0082 (27); −2.4241 (0.4); −2.6703 (0.5) 625 1.24 625:¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0900 (1.0); 9.0696 (1.1); 8.5142(4.0); 8.3294 (1.0); 8.3092 (1.0); 7.7732 (0.5); 7.7612 (2.0); 7.7455(1.8); 7.6202 (3.0); 7.6160 (7.0); 7.6102 (2.8); 7.6064 (1.8); 7.5945(2.0); 7.5821 (1.0); 7.5610 (1.1); 7.5428 (0.8); 7.2876 (1.0); 7.2700(1.0); 7.1885 (0.5); 7.1848 (0.5); 7.1681 (1.0); 7.1501 (0.6); 7.1463(0.6); 7.1283 (2.2); 6.9241 (0.7); 6.9055 (1.3); 6.8866 (0.7); 6.8599(2.3); 6.8053 (1.4); 6.7852 (1.3); 5.7568 (16.0); 5.2445 (0.6); 5.2257(0.6); 4.3461 (0.9); 4.3314 (2.0); 4.3165 (1.0); 4.2612 (1.0); 4.2481(1.7); 4.2348 (1.1); 3.7783 (1.0); 3.7693 (0.9); 3.7633 (0.9); 3.3256(11.9); 3.1318 (1.5); 2.5236 (0.7); 2.5101 (19.3); 2.5058 (40.5); 2.5013(54.2); 2.4968 (38.5); 2.4925 (18.1); 2.1600 (0.3); 2.1388 (0.5); 2.1255(0.5); 2.0744 (0.4); 2.0394 (0.4); 2.0254 (0.5); 2.0027 (0.3); 0.0079(0.7); −0.0002 (21.3); −0.0084 (0.7) 629 2.09 629: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 8.9739 (1.9); 8.9538 (1.9); 8.5544 (0.4); 8.3842 (2.7);8.3611 (3.0); 8.3534 (6.7); 7.8907 (1.2); 7.8785 (1.2); 7.6553 (3.6);7.6515 (2.8); 7.6466 (4.6); 7.6418 (2.6); 7.6325 (3.3); 7.3204 (1.6);7.2981 (2.8); 7.2783 (1.9); 7.1724 (0.9); 7.1505 (1.7); 7.1331 (12);7.1292 (1.1); 6.9069 (1.3); 6.8885 (2.2); 6.8727 (1.1); 6.7876 (2.5);6.7691 (2.1); 5.2365 (0.6); 5.2227 (1.1); 5.2020 (1.0); 5.1865 (0.5);4.2514 (1.9); 4.2395 (3.2); 4.2256 (1.8); 3.3205 (162.9); 3.0650 (1.7);3.0510 (6.7); 3.0385 (6.8); 2.6746 (1.3); 2.6702 (1.7); 2.6658 (1.3);2.5456 (0.4); 2.5233 (4.5); 2.5098 (111.1); 2.5055 (228.2); 2.5011(302.5); 2.4966 (215.4); 2.4923 (102.0); 2.3324 (1.2); 2.3278 (1.7);2.3236 (1.2); 2.1786 (0.4); 2.1705 (0.6); 2.1564 (0.7); 2.1345 (0.8);2.1206 (0.8); 2.1072 (0.3); 2.0227 (0.7); 2.0119 (0.9); 1.9896 (0.6);1.9757 (0.6); 1.3975 (16.0); 1.2981 (0.4); 1.2580 (0.6); 1.2351 (3.6);0.8536 (0.5); 0.0078 (1.2); −0.0002 (36.1); −0.0084 (1.4) 630 5.59 630:¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0221 (2.2); 9.0014 (2.2); 8.6578(9.6); 8.2917 (3.5); 8.2688 (4.0); 7.7935 (4.4); 7.7706 (4.1); 7.6936(2.7); 7.6889 (5.3); 7.6841 (2.9); 7.3740 (3.2); 7.3575 (3.9); 7.2960(0.5); 7.2779 (1.4); 7.2596 (5.4); 7.2490 (2.8); 7.2439 (2.0); 7.2315(1.8); 7.2267 (1.4); 7.2158 (0.7); 7.2100 (0.7); 6.7934 (0.4); 6.7889(0.4); 5.7565 (13.4); 5.6226 (0.6); 5.6026 (1.6); 5.5824 (1.6); 5.5623(0.6); 3.9150 (0.5); 3.8839 (6.4); 3.8527 (0.5); 3.3624 (0.7); 3.3515(1.3); 3.3314 (2.0); 3.3200 (16.7); 3.2889 (1.5); 3.2793 (2.4); 3.2661(1.7); 3.2475 (1.3); 3.2366 (0.7); 2.6747 (0.4); 2.6701 (0.6); 2.6658(0.4); 2.5236 (1.4); 2.5100 (39.3); 2.5057 (82.0); 2.5012 (109.3);2.4967 (78.5); 2.4924 (37.7); 2.4266 (1.5); 2.4077 (1.6); 2.3956 (1.7);2.3767 (1.5); 2.3323 (0.5); 2.3280 (0.6); 2.3233 (0.5); 1.9885 (0.7);1.8670 (1.4); 1.8451 (1.4); 1.8359 (1.4); 1.8144 (12); 1.3617 (16.0);1.2982 (0.6); 1.2583 (0.8); 1.2329 (1.9); 1.2207 (14.1); 1.1928 (0.4);1.1747 (0.5); 0.8528 (0.3); 0.0081 (0.4); −0.0002 (13.8); −0.0083 (0.5)635 4.08 635: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 16.1140 (0.5); 10.4114(5.2); 9.2742 (4.1); 9.2545 (4.1); 8.6672 (16.0); 8.4984 (0.8); 8.3161(0.7); 8.2805 (5.8); 8.2574 (6.8); 7.9468 (0.5); 7.8498 (0.5); 7.8211(0.5); 7.8071 (1.9); 7.7922 (13.1); 7.7695 (10.8); 7.7494 (1.6); 7.7007(4.7); 7.6894 (5.4); 7.6846 (12.3); 7.6801 (10.0); 7.6549 (0.5); 7.6293(0.5); 7.5660 (2.6); 7.5463 (3.9); 7.5265 (1.9); 7.4103 (0.6); 7.3731(7.7); 7.3420 (0.5); 7.2955 (0.6); 7.2790 (0.5); 7.2579 (0.6); 7.174 8(0.6); 7.1587 (0.5); 6.9763 (2.6); 6.9717 (4.9); 6.9672 (2.8); 6.7934(10.6); 6.7888 (10.5); 5.7571 (3.0); 5.7200 (1.4); 5.7123 (1.4); 5.7007(2.3); 5.6927 (2.3); 5.6827 (1.4); 5.6722 (1.3); 4.2620 (0.6); 3.9041(0.7); 3.8714 (10.6); 3.8595 (8.3); 3.3202 (437.6); 3.2547 (10.3);3.2474 (9.8); 3.2274 (3.3); 3.2003 (3.5); 3.1809 (2.7); 3.0561 (0.6);3.0434 (0.7); 3.0415 (0.8); 3.0359 (1.0); 3.0236 (1.1); 2.6887 (0.9);2.6736 (7.4); 2.6705 (7.5); 2.6653 (7.5); 2.6262 (2.8); 2.6181 (3.1);2.5684 (1.0); 2.5234 (15.1); 2.5055 (828.6); 2.5011 (1116.3); 2.4966(810.8); 2.4925 (396.0); 2.3321 (4.3); 2.3276 (6.2); 2.3235 (4.8);1.6275 (0.5); 1.5493 (0.6); 1.3738 (0.7); 1.3611 (0.6); 1.3526 (0.7);1.3364 (0.7); 1.3137 (0.6); 1.2976 (3.0); 1.2584 (4.5); 1.2492 (1.9);1.2336 (4.7); 1.1866 (0.7); 1.1670 (0.7); 1.1470 (0.5); 0.8837 (0.6);0.8665 (1.0); 0.8532 (1.2); 0.8343 (0.9); 0.7968 (0.5); 0.0080 (3.9);−0.0001 (140.0); −0.0082 (6.0); −0.1495 (0.7) 636 1.89 636: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 8.9971 (1.4); 8.9919 (1.4); 8.9766 (1.4);8.9719 (1.4); 8.5599 (0.3); 8.5003 (0.6); 8.4458 (2.8); 8.4226 (3.0);8.3554 (7.4); 8.3047 (0.3); 8.0757 (1.1); 8.0706 (0.5); 8.0539 (12);7.9316 (0.8); 7.9195 (1.1); 7.9128 (1.1); 7.9002 (0.8); 7.6950 (3.1);7.6724 (3.0); 7.6539 (0.6); 7.6428 (0.5); 7.6285 (0.9); 7.6152 (0.9);7.6017 (0.9); 7.5872 (0.4); 7.5792 (0.4); 7.4949 (0.8); 7.4737 (0.7);7.3020 (1.7); 7.2826 (1.7); 7.1716 (1.2); 7.1510 (2.4); 7.1329 (1.9);7.1156 (0.9); 7.0876 (0.6); 6.9221 (0.3); 6.9074 (1.5); 6.8887 (2.4);6.8702 (1.2); 6.7886 (3.0); 6.7683 (2.6); 5.7565 (1.4); 5.2367 (0.7);5.2226 (1.4); 5.2034 (1.3); 5.1877 (0.6); 4.2500 (2.2); 4.2386 (3.3);4.2272 (2.0); 3.3214 (36.9); 3.0794 (2.4); 3.0597 (4.7); 3.0529 (5.6);3.0474 (5.6); 3.0406 (4.9); 3.0261 (0.9); 2.6705 (0.8); 2.6665 (0.6);2.5422 (0.5); 2.5379 (0.5); 2.5324 (0.4); 2.5238 (1.9); 2.5102 (57.4);2.5061 (114.6); 2.5017 (149.9); 2.4973 (108.3); 2.3331 (0.6); 2.3287(0.8); 2.3240 (0.7); 2.1869 (0.4); 2.1731 (0.8); 2.1589 (0.9); 2.1531(0.7); 2.1394 (0.9); 2.1240 (0.9); 2.1119 (0.4); 2.0419 (0.4); 2.0252(0.8); 2.0171 (0.9); 2.0075 (0.9); 1.9889 (0.9); 1.9713 (0.5); 1.3979(16.0); 1.2984 (0.6); 1.2590 (0.9); 1.2353 (1.0); 1.1749 (0.4); 0.8534(0.4); 0.1464 (0.6); 0.0362 (0.5); 0.0081 (6.1); 0.0000 (147.3); −0.0077(6.7); −0.0332 (0.4); −0.1494 (0.7) 637 637 (Atopisomer 1): ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 8.9812 (3.0); 8.9606 (3.1); 8.5585 (2.1);8.5432 (2.2); 8.5347 (2.2); 8.5195 (2.0); 8.4472 (1.0); 8.3740 (10.8);7.8585 (1.3); 7.8460 (2.4); 7.8330 (1.3); 7.7210 (3.3); 7.7173 (3.5);7.7009 (4.0); 7.6972 (4.0); 7.5268 (2.4); 7.5043 (4.0); 7.4818 (2.7);7.4707 (3.7); 7.4513 (6.4); 7.4315 (3.6); 7.3 428 (4.1); 7.3391 (4.3);7.3237 (3.3); 7.3200 (3.0); 7.2841 (2.8); 7.2656 (3.1); 7.1683 (1.4);7.1645 (1.4); 7.1474 (2.9); 7.1298 (1.8); 7.1259 (1.7); 6.9122 (0.3);6.9043 (2.1); 6.9019 (2.2); 6.8834 (3.6); 6.8671 (1.7); 6.8646 (1.7);6.7869 (4.0); 6.7664 (3.6); 6.5264 (1.2); 5.7564 (10.6); 5.2486 (1.0);5.2332 (1.9); 5.2138 (1.8); 5.1993 (0.8); 4.2563 (3.3); 4.2421 (5.3);4.2296 (3.1); 4.0381 (0.5); 4.0202 (0.5); 3.5676 (1.2); 3.5530 (1.0);3.5354 (3.3); 3.5218 (3.7); 3.5179 (3.7); 3.5043 (3.3); 3.4865 (1.0);3.3244 (162.6); 2.6748 (0.7); 2.6705 (1.0); 2.6659 (0.7); 2.5238 (2.2);2.5189 (3.5); 2.5103 (62.0); 2.5059 (130.8); 2.5015 (175.3); 2.4970(125.4); 2.4927 (59.8); 2.3326 (0.7); 2.3281 (1.0); 2.3240 (0.7); 2.1843(0.4); 2.1710 (0.9); 2.1540 (0.9); 2.1492 (1.0); 2.1351 (1.7); 2.1215(1.5); 2.1070 (0.5); 2.0365 (0.6); 2.0236 (1.4); 2.0079 (1.5); 1.9886(3.0); 1.9756 (0.8); 1.9606 (0.4); 1.3973 (1.0); 1.2982 (0.6); 1.2779(7.4); 1.2600 (16.0); 1.2422 (7.8); 1.2362 (2.8); 1.1924 (0.7); 1.1745(1.4); 1.1568 (0.7); 1.1179 (0.4); 0.1460 (0.7); 0.0079 (5.2); −0.0002(164.7); −0.0085 (6.1); −0.1496 (0.8) 637 2.00 637 (Atopisomer 2):¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.9813 (3.2); 8.9607 (3.1); 8.5586(2.0); 8.5432 (2.5); 8.5346 (2.2); 8.5195 (2.0); 8.4528 (0.5); 8.4472(1.0); 8.3793 (4.0); 8.3740 (10.1); 7.8910 (0.4); 7.8462 (2.8); 7.8341(1.5); 7.7210 (3.6); 7.7173 (3.4); 7.7009 (4.4); 7.6971 (3.8); 7.5269(2.3); 7.5044 (4.0); 7.4817 (2.8); 7.4763 (1.8); 7.4707 (3.8); 7.4564(2.4); 7.4512 (6.1); 7.4370 (1.4); 7.4315 (3.4); 7.3722 (0.4); 7.3429(4.6); 7.3392 (4.1); 7.3238 (3.5); 7.3201 (2.9); 7.2866 (3.1); 7.2675(3.4); 7.1684 (1.7); 7.1647 (1.5); 7.1491 (3.3); 7.1299 (2.1); 7.1260(1.7); 6.9045 (2.3); 6.9017 (2.3); 6.8858 (3.8); 6.8672 (1.8); 6.8647(1.6); 6.7871 (4.2); 6.7666 (3.8); 6.5259 (1.0); 5.7618 (3.4); 5.7564(9.6); 5.2477 (1.1); 5.2335 (2.3); 5.2150 (2.0); 5.1991 (0.8); 4.2561(4.1); 4.2423 (5.9); 4.2302 (3.3); 4.0378 (0.5); 4.0201 (0.5); 3.5734(0.5); 3.5677 (1.2); 3.5530 (1.3); 3.5355 (3.7); 3.5222 (4.6); 3.5181(4.1); 3.5044 (3.6); 3.4867 (1.0); 3.3292 (56.4); 3.3241 (147.2); 2.6749(1.0); 2.6704 (1.0); 2.5100 (97.7); 2.5060 (162.3); 2.5014 (184.8);2.4969 (125.4); 2.3326 (0.9); 2.32 82 (1.0); 2.1711 (1.0); 2.1543 (1.2);2.1482 (1.2); 2.1349 (1.8); 2.1213 (1.6); 2.1069 (0.6); 2.0234 (1.7);2.0079 (1.8); 1.9942 (1.9); 1.9885 (3.2); 1.9758 (1.0); 1.3973 (1.0);1.2984 (0.7); 1.2778 (7.7); 1.2650 (7.0); 1.2599 (16.0); 1.2421 (8.2);1.1924 (0.8); 1.1803 (0.7); 1.1746 (1.4); 1.1624 (0.5); 1.1566 (0.8);1.1175 (0.4); 0.8531 (0.3); 0.1461 (0.7); 0.0054 (57.5); −0.0002(161.4); −0.0084 (7.7); −0.1496 (0.7) 638 2.23 638: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 9.0008 (3.2); 8.9802 (3.2); 8.5200 (2.1); 8.5049 (2.3);8.4962 (2.3); 8.4812 (2.3); 8.4700 (11.1); 7.9621 (1.4); 7.9491 (2.6);7.9360 (1.4); 7.656 9 (3.9); 7.6521 (7.7); 7.6473 (4.4); 7.5206 (2.6);7.4975 (4.7); 7.4688 (12.2); 7.4645 (11.6); 7.2968 (3.0); 7.2782 (32);7.1784 (1.5); 7.1750 (1.5); 7.1575 (3.0); 7.1400 (1.9); 7.1363 (1.8);6.9153 (2.2); 6.8968 (3.8); 6.8803 (1.8); 6.8780 (1.8); 6.7978 (4.2);6.7776 (3.9); 5.7568 (14.4); 5.2612 (0.8); 5.2462 (1.9); 5.2271 (1.9);52124 (0.8); 4.2879 (0.4); 4.2684 (2.9); 4.2535 (5.0); 4.2416 (3.2);4.2248 (0.4); 4.0559 (0.5); 4.0381 (1.4); 4.0204 (1.4); 4.0025 (0.5);3.5657 (1.0); 3.5479 (3.4); 3.5341 (3.8); 3.5305 (3.9); 3.5167 (3.4);3.4992 (1.0); 3.3244 (45.5); 2.6751 (0.3); 2.6708 (0.4); 2.6664 (0.3);2.5240 (1.0); 2.5062 (58.1); 2.5018 (77.3); 2.4974 (55.4); 2.4933(26.6); 2.3284 (0.4); 2.3242 (0.3); 2.1917 (0.4); 2.1800 (0.8); 2.1675(0.8); 2.1582 (1.0); 2.1439 (1.7); 2.1299 (1.4); 2.1160 (0.6); 2.0571(0.6); 2.0444 (1.4); 2.0300 (1.4); 2.0168 (0.9); 2.0079 (1.0); 1.9976(0.8); 1.9889 (6.3); 1.3966 (2.5); 1.2716 (7.6); 1.2537 (16.0); 1.2359(7.6); 1.1928 (1.6); 1.1750 (3.2); 1.1572 (1.6); 1.1006 (0.4); 0.1459(0.4); 0.0078 (2.9); −0.0002 (85.1); −0.0085 (3.2); −0.1498 (0.4) 6392.03 639: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0037 (3.5); 8.9833 (3.6);8.5928 (2.3); 8.5776 (2.5); 8.5692 (2.5); 8.5540 (2.3); 8.4447 (8.2);7.9683 (0.9); 7.9555 (1.6); 7.9411 (1.6); 7.9269 (1.7); 7.9141 (0.9);7.6638 (0.8); 7.6566 (0.8); 7.6367 (1.6); 7.6280 (1.5); 7.6154 (1.5);7.6000 (0.8); 7.5928 (0.6); 7.5575 (2.4); 7.5348 (4.5); 7.5123 (2.4);7.2980 (3.6); 7.2784 (4.0); 7.2281 (1.0); 7.2073 (1.8); 7.1856 (1.1);7.1760 (2.3); 7.1556 (3.8); 7.1373 (2.3); 6.9128 (2.6); 6.8941 (4.4);6.8755 (2.1); 6.7945 (5.2); 6.7742 (4.7); 5.7562 (7.5); 5.2574 (1.0);5.2421 (2.3); 5.2232 (2.3); 5.2089 (1.0); 4.2637 (3.6); 4.2504 (6.3);4.2383 (3.7); 4.0560 (0.4); 4.0382 (12); 4.0202 (1.2); 4.0029 (0.4);3.5615 (0.9); 3.5447 (2.8); 3.5317 (4.0); 3.5142 (2.9); 3.3254 (108.5);2.6706 (0.7); 2.5017 (124.2); 2.3283 (0.7); 2.1918 (0.5); 2.1788 (1.1);2.1587 (1.2); 2.1432 (2.0); 2.1298 (1.7); 2.1157 (0.7); 2.0354 (1.5);2.0224 (1.6); 2 0015 (1.1); 1.9 887 (6.0); 1.3972 (0.8); 1.2987 (0.3);1.2755 (7.7); 1.2577 (16.0); 1.2399 (8.0); 1.1925 (1.4); 1.1748 (2.8);1.1570 (1.4); 1.1112 (0.4); 0.1461 (0.5); −0.0003 (106.4); −0.1497 (0.5)640 2.48 640: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0190 (2.7); 8.9986(2.8); 8.5860 (1.9); 8.5708 (1.8); 8.5624 (1.9); 8.5471 (1.6); 8.4880(8.4); 8.4794 (1.3); 8.4515 (0.7); 8.4433 (0.4); 8.2878 (0.5); 8.2279(2.1); 8.0387 (1.2); 8.0254 (2.1); 8.0125 (1.1); 7.7914 (0.8); 7.6916(16.0); 7.5748 (0.5); 7.5631 (1.8); 7.5519 (0.4); 7.5398 (3.4); 7.5166(1.7); 7.2969 (2.4); 7.2786 (2.7); 7.1814 (1.1); 7.1778 (1.2); 7.1606(2.5); 7.1428 (1.6); 6.9190 (1.7); 6.9002 (3.0); 6.8820 (1.5); 6.7996(3.4); 6.7792 (3.1); 5.7563 (6.7); 5.2566 (0.7); 5.2422 (1.7); 5.2228(1.7); 5.2079 (0.8); 4.2673 (2.5); 4.2530 (4.4); 4.2411 (2.9); 4.0382(0.5); 4.0200 (0.5); 3.5675 (1.1); 3.5501 (2.9); 3.5331 (3.2); 3.5189(2.7); 3.5015 (0.8); 3.3250 (141.3); 2.6708 (0.8); 2.5059 (106.3);2.5018 (136.0); 2.4976 (97.9); 2.3285 (0.7); 2.1793 (0.7); 2.1585 (0.9);2.1438 (1.4); 2.1299 (12); 2.1166 (0.5); 2.0576 (0.5); 2.0442 (12);2.0302 (1.3); 2.0171 (0.8); 2.0082 (0.9); 1.9888 (2.3); 1.3974 (1.0);1.2982 (0.3); 12718 (5.9); 1.2620 (2.4); 1.2539 (12.0); 12362 (6.0);1.1928 (0.6); 1.1750 (1.1); 1.1571 (0.6); −0.1461 (0.6); 0.0073 (4.4);−0.0001 (110.9); −0.0082 (4.5); −0.1496 (0.6) 641 1.92 641: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.0727 (0.5); 9.0637 (0.6); 9.0525 (0.6);8.4190 (0.8); 8.4096 (1.8); 8.4004 (2.2); 7.7346 (0.4); 7.6795 (1.2);7.6757 (1.2); 7.6593 (1.2); 7.6558 (1.2); 7.5940 (0.5); 7.5815 (2.6);7.5618 (1.4); 7.5440 (0.4); 7.4389 (0.5); 7.4315 (0.5); 7.4194 (0.9);7.4111 (0.8); 7.4002 (0.5); 7.3915 (0.5); 7.3174 (0.7); 7.3021 (1.5);7.2863 (1.2); 7.1704 (0.5); 7.1530 (1.0); 7.1323 (0.6); 6.9077 (0.7);6.8882 (1.2); 6.8702 (0.6); 6.7922 (1.4); 6.7715 (1.2); 5.2376 (0.6);5.2210 (0.6); 4.2559 (2.4); 4.2484 (2.3); 3.7210 (1.1); 3.7090 (0.9);3.3195 (59.6); 2.6702 (1.5); 2.5231 (3.5); 2.5054 (198.0); 2.5011(259.6); 2.4968 (186.2); 2.3320 (1.1); 2.3277 (1.5); 2.1827 (0.3);2.1601 (0.4); 2.1464 (0.6); 2.1325 (0.5); 2.0385 (0.4); 2.0240 (0.5);1.9970 (11.1); 1.9022 (1.6); 1.3977 (16.0); 0.1461 (1.0); 0.0077 (7.6);−0.0002 (219.7); −0.0081 (8.5); −0.1498 (1.1) 644 2.03 644: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.1762 (2.1); 9.1562 (2.2); 8.6798 (7.4);7.9799 (1.3); 7.9643 (1.5); 7.9565 (1.5); 7.9407 (1.4); 7.6877 (2.4);7.6832 (4.5); 7.6479 (3.0); 7.5660 (1.5); 7.5426 (2.8); 7.5196 (1.4);7.4951 (8.0); 7.4914 (7.9); 7.3265 (2.0); 7.3076 (2.2); 7.1882 (1.1);7.1662 (4.4); 7.1530 (1.6); 6.9288 (1.5); 6.9104 (2.5); 6.8919 (1.2);6.8417 (3.1); 6.8047 (2.9); 6.7842 (2.6); 5.2372 (0.6); 5.2226 (1.3);5.2037 (1.3); 5.1892 (0.6); 4.3111 (2.0); 4.2962 (4.0); 4.2811 (2.3);4.2538 (1.2); 4.2359 (1.7); 4.2269 (1.8); 4.2119 (1.1); 4.2052 (1.3);4.1841 (0.4); 4.0378 (0.5); 4.0200 (0.6); 3.5379 (2.0); 3.5229 (3.8);3.5078 (1.9); 3.3232 (6.1); 3.0749 (16.0); 2.8662 (2.9); 2.6705 (0.7);2.5480 (0.8); 2.5053 (97.3); 2.5014 (124.4); 2.3284 (0.7); 2.2069 (0.4);2.1981 (0.6); 2.1838 (0.8); 2.1745 (0.8); 2.1629 (0.8); 2.1517 (0.6);2.0745 (3.5); 2.0303 (0.9); 2.0162 (0.7); 2.0025 (0.6); 1.9887 (2.6);1.2341 (0.9); 1.1924 (0.6); 1.1746 (1.2); 1.1568 (0.6); −0.0001 (61.3)647 3.90 647: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.2469 (1.6); 9.2267(1.7); 8.7138 (6.9); 8.4548 (3.2); 8.3695 (1.3); 8.3539 (1.4); 8.3458(1.4); 8.3303 (1.3); 7.7363 (2.2); 7.7312 (2.4); 7.6970 (2.2); 7.6921(4.6); 7.6877 (3.4); 7.6656 (2.6); 7.6424 (1.4); 7.6381 (0.9); 7.6330(1.2); 7.6280 (0.6); 7.5214 (6.3); 7.5172 (6.1); 7.3823 (1.5); 7.3649(1.6); 7.1937 (0.8); 7.1902 (0.8); 7.1726 (1.6); 7.1552 (1.0); 7.1517(1.0); 6.9391 (1.1); 6.9366 (1.2); 6.9180 (2.0); 6.9019 (1.0); 6.8993(1.0); 6.8088 (2 2); 6.8068 (2.2); 6.7884 (2.0); 6.7863 (2.0); 5.7561(12.1); 5.2495 (0.4); 5.2362 (1.0); 5.2167 (1.0); 5.2022 (0.5); 4.2875(0.3); 4.2695 (0.9); 4.2546 (1.8); 4.2458 (1.6); 4.2339 (0.9); 4.2262(1.0); 4.2061 (0.3); 4.0558 (0.6); 4.0380 (1.7); 4.0202 (1.7); 4 0024(0.6); 3.7243 (0.9); 3.7057 (2.6); 3.6886 (2.0); 3.6540 (0.4); 3.6195(1.1); 3.6034 (2.2); 3.5864 (1.6); 3.5681 (0.8); 3.5517 (0.4); 3.3229(30.8); 3.0469 (13.3); 3.0228 (0.8); 2.9728 (16.0); 2.9526 (0.6); 2.6705(0.4); 2.5240 (0.9); 2.5104 (24.8); 2.5061 (52.1); 2.5016 (69.8); 2.4971(49.8); 2.4928 (23.6); 2.3283 (0.4); 2.2263 (0.3); 2.2177 (0.4); 2.2054(0.6); 2.1949 (0.6); 2.1835 (0.7); 2.1718 (0.5); 2.0912 (0.5); 2.0835(0.6); 2.0764 (0.8); 2.0614 (0.5); 2.0499 (0.5); 2.0418 (0.5); 1.9888(7.6); 1.1927 (2.0); 1.1749 (4.0); 1.1571 (1.9); 0.0079 (0.6); −0.0002(19.9); −0.0085 (0.7) 648 2.06 648: ¹H-NMR (400.0 MHz, d₆-DMSO): δ =9.0572 (2.9); 9.0367 (2.9); 8.4493 (10.6); 8.1700 (2.0); 8.1550 (2.1);8.1463 (2.1); 8.1314 (2.0); 7.7358 (0.7); 7.7309 (0.8); 7.6651 (3.6);7.6604 (7.0); 7.6556 (4.0); 7.6378 (0.4); 7.6329 (0.5); 7.4698 (11.0);7.4663 (10.8); 7.4519 (2.4); 7.4287 (4.1); 7.4056 (2.1); 7.3170 (2.8);7.2990 (3.1); 7.1870 (1.4); 7.1840 (1.4); 7.1665 (2.9); 7.1487 (1.8);7.1452 (1.7); 6.9224 (2.0); 6.9044 (3.5); 6.8874 (1.7); 6.8060 (4.0);6.7857 (3.6); 5.7560 (16.0); 5.5709 (0.8); 5.5640 (1.0); 5.5582 (0.9);5.4176 (1.0); 5.2110 (0.8); 5.1968 (1.8); 5.1775 (1.8); 5.1628 (0.8);4.7415 (0.4); 4.7258 (0.5); 4.7120 (0.9); 4.6976 (0.9); 4.6840 (0.9);4.6565 (3.0); 4.6425 (1.9); 4.6234 (1.6); 4.6147 (1.7); 4.5979 (2.4);4.5899 (2.1); 4.5582 (1.4); 4.5287 (0.6); 4.2661 (3.1); 4.2539 (5.1);4.2399 (3.1); 4.0569 (0.6); 4.0380 (1.8); 4.0202 (1.8); 4.0026 (0.6);3.3241 (88.4); 3.0496 (0.4); 2.6708 (0.7); 2.5060 (93.6); 2.5017(121.8); 2.4974 (88.1); 2.3287 (0.7); 2.2024 (0.4); 2.1879 (1.0); 2.1736(1.1); 2.1537 (1.3); 2.1387 (1.3); 2.1252 (0.5); 2.0539 (0.6); 2.0402(1.2); 2.0284 (1.4); 2.0149 (0.9); 2.0067 (1.0); 1.9888 (8.4); 1.3973(2.6); 1.1928 (2.1); 1.1750 (4.1); 1.1572 (2.0); 0.0080 (1.0); −0.0001(30.3) 649 3.76 649: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.3085 (1.9);9.2880 (2.0); 8.6476 (8.2); 8.3888 (1.4); 8.3732 (1.6); 8.3651 (1.6);8.3496 (1.5); 8.1547 (0.5); 7.6899 (2.7); 7.6851 (5.2); 7.6803 (2.9);7.6387 (1.6); 7.6155 (3.1); 7.5923 (1.6); 7.5128 (7.7); 7.5088 (7.6);7.3587 (2.0); 7.3408 (2.1); 7.1945 (0.9); 7.1910 (1.0); 7.1736 (2.0);7.1559 (1.2); 7.1525 (1.2); 6.9340 (1.5); 6.9157 (2.4); 6.8992 (1.2);6.8968 (1.2); 6.8099 (2.7); 6.7897 (2.5); 5.2926 (0.5); 5.2790 (1.2);5.2593 (1.2); 5.2449 (0 6); 5.1397 (1.0); 5.1247 (2.2); 5.1092 (1.0);4.3009 (0.4); 4.2935 (0.4); 4.2812 (1.1); 4.2719 (1.1); 4.2537 (1.6);4.2400 (1.0); 4.2326 (1.2); 4.2124 (0.4); 4.2051 (0.3); 4.0377 (0.8);4.0200 (0.8); 3.6455 (0.8); 3.6328 (2.3); 3.6195 (2.5); 3.6063 (12);3.5285 (2.3); 3.5160 (3.1); 3.5041 (1.4); 3.3211 (12.7); 3.0487 (16.0);2.6747 (0.4); 2.6700 (0.6); 2.6660 (0.4); 2.5234 (1.3); 2.5097 (37.4);2.5056 (78.3); 2.5011 (104.9); 2.4967 (76.0); 2.3324 (0.4); 2.3278(0.6); 2.3234 (0.5); 2.2371 (0.4); 2.2287 (0.5); 22165 (0.8); 2.2074(0.8); 2.1953 (0.8); 2.1839 (0.6); 2.1748 (0.4); 2.0742 (9.8); 2.0583(0.7); 2.0518 (0.7); 20411 (0.6); 20328 (0.6); 1.9885 (3.7); 1.1924(1.0); 1.1746 (1.9); 1.1568 (0, 9); 0.0079 (0.6); −0.0003 (20.1);−0.0085 (0.8) 650 4.51 650: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1837(1.2); 9.1634 (1.3); 8.6809 (4.8); 8.2435 (0.9); 8.2277 (1.0); 8.2197(1.0); 8.2043 (1.0); 7.6933 (1.4); 7.6887 (2.8); 7.6837 (2.0); 7.6575(1.9); 7.6343 (0.9); 7.5177 (4.8); 7.5133 (4.7); 7.3620 (1.2); 7.3438(1.3); 7.1910 (0.6); 7.1874 (0.6); 7.1697 (12); 7.1524 (0.8); 7.1492(0.7); 6.9344 (0.9); 6.9161 (1.5); 6.8981 (0.7); 6.8052 (1.7); 6.7851(1.5); 5.7556 (7.6); 5.2537 (0.3); 5.2391 (0.8); 5.2201 (0.8); 5.2061(0.3); 4.2758 (0.7); 4.2596 (1.2); 4.2506 (1.2); 4.2386 (0.7); 4.2304(0.8); 3.5520 (1.3); 3.5365 (16.0); 3.5178 (1.3); 3.3250 (452); 3.0097(10.2); 2.7359 (1.0); 2.7216 (1.8); 2.7177 (1.9); 2.7048 (0.9); 2.7002(0.9); 2.5236 (0.6); 2.5059 (34.1); 2.5017 (45.7); 2.4974 (33.7); 2.2010(0.5); 2.1907 (0.5); 2.1792 (0.5); 2.1683 (0.4); 2.0735 (0.3); 2.0661(0.4); 2.0583 (0.5); 2.0435 (0.4); 2.0318 (0.4); 2.0234 (0.4); 0.0074(0.6); −0.0002 (16.6); −0.0080 (0.7) 661 3.48 661: ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 9.2660 (1.8); 9.2458 (1.8); 8.7364 (6.3); 8.4266 (1.2);8.4110 (1.3); 8.4029 (1.3); 8.3875 (1.3); 7.7469 (11.3); 7.7294 (1.3);7.7061 (2.5); 7.6829 (1.3); 7.3840 (1.6); 7.3651 (1.8); 7.1922 (0.8);7.1746 (1.7); 7.1566 (1.0); 7.1535 (1.0); 6.9384 (1.2); 6.9200 (2.1);6.9014 (1.0); 6.8085 (2.4); 6.7883 (2.1); 5.2480 l (0.5); 5.2343 (1.0);5.2148 (1.1); 5.2011 (0.5); 4.2879 (0.3); 4.2693 (0.9); 4.2543 (1.8);4.2453 (1.7); 4.2331 (0.9); 4.2256 (1.1); 4 2045 (0.3); 3.7270 (1.0);3.7089 (2.8); 3.6921 (2.1); 3.6562 (0.3); 3.6219 (1.1); 3.6061 (2.4);3.5891 (1.7); 3.5707 (0.8); 3.3195 (31.5); 3.0513 (13.4); 2.9714 (16.0);2.6701 (0.4); 2.5050 (45.4); 2.5008 (60.1); 2.4965 (44.9); 2.3276 (0.4);2.2270 (0.4); 2.2193 (0.4); 2.2055 (0.6); 2.1953 (0.7); 2.1842 (0.7);2.1722 (0.5); 2.0920 (0.5); 2.0848 (0.7); 2.0775 (0.8); 2.0634 (0.6);2.0509 (0.5); 2.0426 (0.5); 0.0077 (2.0); −0.0002 (58.4); −0.0083 (3.0)666 4.19 666: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.1886 (0.4); 9.1756(2.0); 9.1551 (2.1); 8.8415 (0.9); 8.6572 (7.6); 8.3810 (1.4); 8.3654(1.5); 8.3574 (1.6); 8.3419 (1.4); 8.1800 (1.9); 7.7145 (0.7); 7.7106(0.7); 7.7059 (0.4); 7.6898 (2.4); 7.6854 (4.3); 7.6809 (2.5); 7.6365(1.6); 7.6133 (3.0); 7.5902 (1.5); 7.5413 (1.0); 7.5373 (0.9); 7.5138(7.7); 7.5099 (7.4); 7.4093 (1.7); 7.3948 (1.9); 7.3893 (1.9); 7.2887(1.0); 7.2836 (1.3); 7.2686 (2.6); 7.2587 (1.1); 7.2540 (1.1); 7.2404(2.9); 7.2351 (3.5); 7.2262 (3.2); 7.2177 (2.7); 7.1992 (0.5); 5.7554(11.4); 5.5865 (0.6); 5.5671 (1.7); 5.5474 (1.8); 5.5277 (0.6); 5.1663(0.3); 4.4586 (0.6); 4.4451 (0.3); 3.6266 (3.1); 3.6152 (2.4); 3.5424(2.7); 3.5304 (3.5); 3.3506 (1.4); 3.2177 (0.4); 3.0483 (16.0); 3.0232(0.8); 3.0095 (0.7); 2.9999 (0.8); 2.9917 (1.0); 2.9833 (1.0); 2.9700(1.0); 2.9614 (0.9); 2.9068 (0.8); 2.8863 (1.6); 2.8662 (1.3); 2.8468(0.9); 2.8263 (0.5); 2.6707 (0.3); 2.569 4 (0.4); 2.5600 (0.5); 2.5497(0.8); 2.5390 (1.1); 2.5290 (1.2); 2.5059 (41.4); 2.5017 (53.0); 2.4974(39.4); 2.3925 (2.1); 2.3288 (0.3); 1.9889 (1.1); 1.9703 (1.1); 1.9596(0.6); 1.9500 (1.1); 1.9391 (1.1); 1.9293 (0.5); 1.9188 (0.9); 1.8974(0.3); 1.2324 (0.6); 1.1749 (0.4); −0.0001 (16.4) 667 2.20 667: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.1838 (0.9); 9.1637 (0.9); 8.6672 (3.8);8.2561 (0.9); 8.2533 (1.0); 8.2348 (1.1); 8.2318 (1.0); 7.8167 (1.1);7.8136 (1.0); 7.7994 (2.0); 7.7952 (1.8); 7.7744 (1.0); 7.7549 (0.4);7.7051 (1.0); 7.6860 (1.3); 7.6714 (1.0); 7.6531 (1.0); 7.6502 (1.1);7.6352 (10.7); 7.5676 (0.6); 7.5485 (1.0); 7.5297 (0.4); 5.7451 (0.3);5.7340 (0.6); 5.7256 (0.6); 5.7149 (0.3); 3.5677 (1.1); 3.3192 (50.0);3.2454 (0.6); 3.2261 (0.7); 3.1987 (0.8); 3.1793 (0.7); 3.0654 (16.0);2.6876 (0.8); 2.6787 (1.0); 2.6704 (0.7); 2.6658 (0.5); 2.6408 (0.7);2.6321 (0.7); 2.5234 (1.7); 2.5056 (81.8); 2.5013 (106.7); 2.4968(76.8); 2.3320 (0.5); 2.3280 (0.6); 2.3241 (0.4); 1.9883 (1.2); 1.3976(5.9); 1.1925 (0.3); 1.1747 (0.7); 1.1568 (0.3); 0.1461 (0.4); 0.0078(3.7); −0.0002 (99.3); −0.0084 (4.0); −0.1496 (0.5) 668 3.94 668: ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.1048 (0.6); 9.0845 (0.6); 8.5684 (2.2);8.2951 (0.9); 8.2722 (1.1); 7.7677 (1.1); 7.7447 (1.0); 7.6197 (2.0);7.3464 (0.6); 7.3272 (0.6); 7.1808 (0.3); 7.1623 (0.6); 7.1415 (0.4);6.9222 (0.4); 6.9036 (0.8); 6.8863 (0.3); 6.7970 (0.8); 6.7766 (0.7);5.2280 (0.4); 5.2096 (0.4); 4.2664 (0.4); 4.2398 (0.5); 4.2239 (0.3);4.2180 (0.4); 3.3213 (197.3); 3.0723 (9.7); 3.0549 (1.1); 2.6700 (1.0);2.5051 (126.7); 2.5011 (167.6); 2.4969 (130.1); 2.3278 (1.0); 1.3975(16.0); 0.1457 (0.6); −0.0003 (133.9); −0.1501 (0.7) 669 2.67 669:¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0888 (1.0); 9.0685 (1.0); 8.5482(3.5); 8.2431 (1.6); 8.2203 (1.8); 7.7361 (1.8); 7.7132 (1.7); 7.3437(1.0); 7.3234 (1.3); 7.2978 (0.9); 7.2924 (0.6); 7.2742 (0.4); 7.1768(0.5); 7.1503 (1.0); 7.1385 (0.6); 7.0392 (1.0); 7.0204 (1.0); 6.9196(0.7); 6.9008 (1.2); 6.8822 (0.6); 6.7944 (1.4); 6.7741 (1.2); 5.2331(0.7); 5.2138 (0.6); 4.2661 (0.6); 4.2491 (0.9); 4.2400 (1.0); 4.2265(0.6); 4.2192 (0.7); 3.3208 (107.7); 3.0636 (16.0); 2.6703 (0.9); 2.5052(108.3); 2.5012 (145.2); 2.4972 (117.6); 2.3278 (0.9); 2.1920 (0.4);2.1823 (0.4); 2.1690 (0.4); 2.0407 (0.4); 2.0341 (0.5); 20229 (0.4);2.0072 (0.3); 1.3976 (2.0); 0.1458 (0.5); −0.0002 (112.9); −0.1499 (0.5)670 2.84 670: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0781 (0.7); 9.0580(0.8); 8.5100 (2.0); 8.1805 (1.6); 8.1576 (1.9); 7.6967 (2.0); 7.6738(1.8); 7.3393 (0.8); 7.3205 (0.9); 7.2257 (1.6); 7.1779 (0.4); 7.1741(0.4); 7.1563 (0.8); 7.1392 (0.5); 7.1353 (0.5); 7.0548 (0.5); 7.0243(0.5); 6.9152 (0.7); 6.8967 (1.1); 6.8779 (0.6); 6.8661 (0.5); 6.8407(0.5); 6.7933 (1.2); 6.7749 (1.1); 5.7551 (0.4); 5.2322 (0.5); 5.2138(0.5); 4.2667 (0.5); 4.2575 (0.5); 4.2498 (0.6); 4.2380 (0.7); 4.2252(0.4); 4.2173 (0.6); 3.5677 (5.0); 3.3190 (47.9); 3.0537 (16.0); 2.6747(0.4); 2.6701 (0.6); 2.6656 (0.4); 2.5235 (1.3); 2.5099 (32.8); 2.5056(69.2); 2.5011 (93.6); 2.4966 (68.7); 2.4922 (34.2); 2.3633 (0.6);2.3451 (2.6); 2.3280 (0.8); 2.323S (0.6); 2.1902 (0.4); 2.1802 (0.3);2.1680 (0.3); 2.0341 (0.4); 1.3975 (0.9); 1.3203 (1.7); 1.2826 (8.0);0.8894 (0.7); 0.1460 (0.4); 0.0079 (3.1); −0.0002 (94.5); −0.0084 (4.2);−0.1497 (0.4) 671 3.00 671: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0854(0.5); 9.0650 (0.5); 8.6944 (0.6); 8.5236 (3.9); 8.2521 (1.7); 8.2292(1.8); 7.7986 (0.6); 7.7790 (1.0); 7.7534 (1.9); 7.7395 (0.5); 7.7304(2.0); 7.7225 (1.0); 7.7009 (0.6); 7.6084 (0.8); 7.3380 (0.8); 7.3199(0.9); 7.1766 (0.5); 7.1728 (0.4); 7.1553 (0.9); 7.1381 (0.5); 7.1340(0.5); 6.9150 (0.6); 6.8944 (1.0); 6.8759 (0.5); 6.7934 (1.3); 6.7728(1.1); 5.7556 (0.5); 5.2278 (0.6); 5.2078 (0.6); 4.2631 (0.6); 4.2545(0.6); 4.2459 (0.7); 4.2376 (0.8); 4.2136 (0.5); 3.3202 (122.1); 3.0699(16.0); 3.0549 (2.9); 2.6746 (0.7); 2.6700 (0.9); 2.6656 (0.7); 2.5233(2.3); 2.5098 (55.6); 2.5055 (115.1); 2.5011 (154.0); 2.4966 (112.5);2.4923 (56.1); 2.3322 (0.6); 2.3278 (0.9); 2.3234 (0.7); 2.1869 (0.4);2.1780 (0.4); 2.1659 (0.4); 2.0309 (0.4); 0.8892 (0.7); 0.1457 (0.7);0.0077 (4.8); −0.0002 (143.2); −0 0084 (6.6); −0.1498 (0.7) 672 2.20672: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0722 (0.4); 9.0608 (0.9); 9.0405(0.9); 8.5074 (3.8); 8.1786 (1.6); 8.1557 (1.9); 7.6922 (1.9); 7.6693(1.8); 7.3389 (0.8); 7.3198 (0.9); 7.1783 (0.4); 7.1747 (0.4); 7.1572(0.8); 7.1400 (0.5); 7.1359 (0.5); 7.0250 (1.5); 6.9161 (0.6); 6.8975(1.1); 6.8814 (0.5); 6.8787 (0.5); 6.8394 (1.0); 6.8085 (1.0); 6.7953(1.3); 6.7748 (1.1); 6.3561 (0.3); 5.2342 (0.5); 5.2146 (0.5); 4.2667(0.5); 4.2568 (0.5); 4.2498 (0.7); 4.2396 (0.8); 4.2261 (0.5); 4.2188(0.6); 3.3229 (33.8); 3.0542 (16.0); 2.5234 (0.5); 2.5097 (11.7); 2.5056(24.2); 2.5011 (32.4); 2.4966 (23.8); 2.4923 (11.9); 2.3130 (4.7);2.3061 (4.8); 2.1910 (0.3); 2.1813 (0.4); 2.1686 (0.4); 2.1573 (1.8);2.0410 (0.3); 2.0334 (0.4); 1.2344 (0.4); 0.0079 (1.1); −0.0002 (31.5);−0.0084 (1.4) 673 2.73 673: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.0829(2.0); 9.0626 (2.0); 8.4835 (6.9); 8.4575 (1.2); 8.4426 (1.3); 8.4336(1.3); 8.4188 (1.2); 7.8687 (0.8); 7.8560 (1.6); 7.8426 (0.8); 7.6931(16.0); 7.5995 (1.6); 7.5762 (3.1); 7.5529 (2.2); 7.5258 (0.6); 7.5058(0.5); 7.4980 (0.5); 7.4886 (0.4); 7.4803 (0.5); 7.4548 (3.8); 7.4504(3.9); 7.2728 (1.8); 7.2546 (1.9); 7.1790 (0.9); 7.1752 (0.9); 7.1581(1.8); 7.1405 (1.2); 7.1365 (1.1); 6.9004 (1.4); 6.8818 (2.3); 6.8654(1.0); 6.8631 (1.1); 6.7942 (2.6); 6.7756 (2.3); 6.2176 (2.4); 6.2126(4.3); 6.2077 (2.5); 5.7555 (10.1); 5.2284 (0.5); 5.2139 (1.2); 5.1949(1.2); 5.1806 (0.5); 4.4965 (0.6); 4.4922 (0.6); 4.4773 (1.9); 4.4617(4.2); 4.4463 (2.1); 4.2421 (1.9); 4.2296 (3.2); 4.2156 (2.5); 3.8610(1.0); 3.8460 (2.6); 3.8316 (2.5); 3.8166 (0.9); 3.3249 (29.4); 2.6705(0.3); 2.5239 (0.8); 2.5189 (1.2); 2.5103 (18.1); 2.5061 (37.6); 2.5017(50.5); 2.4972 (37.0); 2.4929 (18.4); 2.1465 (0.6); 2.1327 (0.6); 2.1260(0.6); 2.1119 (0.9); 2.0972 (0.9); 2.0828 (0.3); 2.0328 (0.4); 2.0199(0.8); 2.0077 (0.9); 1.9943 (0.6); 1.9858 (0.6); 1.9715 (0.5); 1.3520(0.8); 1.2586 (0.4); 1.2276 (0.9); 0.0072 (2.0); −0.0002 (60.0); −0.0084(2.8) 674 4.13 674: ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 9.2997 (1.7);9.2792 (1.7); 8.6010 (6.9); 8.3134 (2.8); 8.2904 (3.1); 7.7458 (3.3);7.7229 (3.2); 7.6789 (2.2); 7.6743 (4.1); 7.6696 (2.4); 7.6590 (0.4);7.6355 (0.7); 7.5524 (0.4); 7.3767 (1.8); 7.3464 (1.8); 7.3278 (1.8);7.1892 (0.9); 7.1856 (0.9); 7.1683 (1.7); 7.1509 (1.1); 7.1473 (1.0);6.9239 (1.2); 6.9054 (2.1); 6.8889 (1.0); 6.8866 (1.0); 6.8042 (2.4);6.7835 (2.0); 5.7555 (1.3); 5.2834 (0.5); 5.2687 (1.0); 5.2494 (1.1);5.2346 (0.6); 5.1224 (1.1); 5.1071 (2.5); 5.0920 (1.1); 4.2941 (0.5);4.2867 (0.5); 4.2744 (1.1); 4.2654 (1.0); 4.2580 (1.2); 4.2502 (1.4);4.2432 (1.2); 4.2303 (0.9); 4.2227 (1.1); 4.2024 (0.4); 4.1950 (0.3);3.7342 (0.3); 3.7229 (0.4); 3.7106 (0.4); 3.6435 (0.8); 3.6309 (2.1);3.6172 (2.4); 3.6039 (1.3); 3.5678 (16.0); 3.5277 (2.0); 3.5149 (2.7);3.5038 (1.3); 3.3194 (58.5); 3.0752 (0.5); 3.0653 (1.3); 3.0459 (13.7);2.6748 (0.7); 2.6702 (1.0); 2.6658 (0.7); 2.5097 (63.1); 2.5057 (123.7);2.5013 (161.6); 2.4968 (118.2); 2.3325 (0.7); 2.3281 (0.9); 2.3237(0.7); 2.2229 (0.5); 2.2097 (0.7); 2.2002 (0.7); 2.188 2 (0.8); 2.1771(0.6); 2.1664 (0.4); 2.0605 (0.7); 2.0529 (0.8); 2.0428 (0.6); 2.0365(0.6); 2.0267 (0.6); 2.0185 (0.6); 1.2586 (0.5); 1.2492 (0.6); 1.2355(1.6); 0.1461 (0.6); 0.0077 (5.9); 0.0000 (131.3); −0.0081 (7.0);−0.1495 (0.6) 377 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.97(s, 1H), 8.22 (m, 1H), 8.09 (d, J = L2): 1.1 Hz, 1H), 7.68 (d, J = 6.3Hz, 1H), R_(t) = 2.83 7.60 (m, 1H), 7.29 (d, J = 7.4 Hz, 1H), min;7.26-7.16 (m, 2H), 6.96-6.81 (m, m/z = 473 3H), 5.41-5.33 (m, 1H), 4.34(m, 1H), [M + H]⁺. 4.19 (m, 1H), 3.96 (s, 3H), 3.13 (s, 6H), 2.44-2.33(m, 1H), 2.25-2.15 (m, 1H). 378 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.91 (s, 1H), 8.77 (d, J = 5.0 Hz, 1H), L2): 8.25 (m, 1H), 8.03(s, 1H), 7.79 (m, R_(t) = 2.82 1H), 7.72 (m, 1H), 7.67-7.59 (m, 1H),min; 7.31 (d, J = 7.3 Hz, 1H), 7.24-7.17 (m, m/z = 450 1H), 7.13 (d, J =7.5 Hz, 1H), 6.98- [M + H]⁺. 6.90 (m, 1H), 6.87 (d, J = 8.2 Hz, 1H),5.37 (q, J = 5.4 Hz, 1H), 4.35 (m, 1H), 4.21 (m, 1H), 3.15 (s, 6H),2.46-2.34 (m, 1H), 2.22 (m, 1H). 379 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 9.01 (s, 1H), 8.15 (t, J = 6.3 Hz, 2H), L2):7.68 (d, J = 6.3 Hz, 1H), 7.62-7.54 (m, R_(t) = 2.08 1H), 7.41 (d, J =7.3 Hz, 1H), 7.30 (d, J = min; 7.5 Hz, 1H), 7.21 (t, J = 7.7 Hz, 1H),m/z = 440 6.90 (m, 3H), 6.76 (s, 1H), 5.38 (q, J = [M + H]⁺. 5.4 Hz,1H), 4.48 (s, 2H), 4.35 (m, 1H), 4.25-4.16 (m, 1H), 3.12 (s, 6H), 2.39(m, 1H), 2.21 (m, 1H). 380 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 9.00 (s, 1H), 8.58 (d, J = 5.1 Hz, 1H), L2): 8.18 (m, 1H), 7.69(m, 1H), 7.59 (m, R_(t) = 2.24 1H), 7.43-7.28 (m, 4H), 7.24-7.17 (m,min; 1H), 6.97-6.83 (m, 2H), 5.38 (q, J = m/z = 439 5.4 Hz, 1H), 4.35(m, 1H), 4.20 (m, 1H), [M + H]⁺. 3.13 (s, 6H), 2.63 (s, 3H), 2.45-2.34(m, 1H), 2.22 (m, 1H). 381 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.92 (s, 1H), 8.52-8.43 (m, 2H), 8.20 L2): (m, 1H), 7.63-7.56(m, 1H), 7.52 (m, R_(t) = 2.26 1H), 7.31 (m, 2H), 7.23-7.17 (m, 1H),min; 7.14 (d, J = 4.8 Hz, 1H), 6.96-6.82 (m, m/z = 439 2H), 5.37 (q, J =5.4 Hz, 1H), 4.34 (m, [M + H]⁺. 1H), 4.19 (m, 1H), 3.15 (s, 6H), 2.38 (m1H), 2.26-2.15 (m, 1H), 2.01 (s, 3H). 382 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.91 (s, 1H), 8.70 (s, 1H), 8.55 (d, J = L2):4.9 Hz, 1H), 8.28-8.20 (m, 1H), 7.65- R_(t) = 2.63 7.57 (m, 2H),7.35-7.27 (m, 2H), 7.24- min; 7.14 (m, 2H), 6.92 (m, 1H), 6.86 (d, J =m/z = 259 8.2 Hz, 1H), 5.41-5.33 (m, 1H), 4.39- [M + H]⁺. 4.29 (m, 1H),4.19 (m, 1H), 3.15 (s, 6H), 2.44-2.33 (m, 1H), 2.20 (m, 1H). 383 LC-MS¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.94 (s, 1H), 8.55 (s, 1H),8.49 (d, J = L2): 4.8 Hz, 1H), 8.23 (m, 1H), 7.70 (d, J = R_(t) = 2.596.9 Hz, 1H), 7.61 (m, 1H), 7.45-7.38 min; (m, 1H), 7.29 (d, J = 7.6 Hz,1H), 7.25 m/z = 443 (d, J = 6.5 Hz, 1H), 7.23-7.16 (m, [M + H]⁺. 1H),6.92 (m, 1H), 6.86 (d, J = 8.2 Hz, 1H), 5.41-5.32 (m, 1H), 4.34 (m, 1H),4.19 (m, 1H), 3.14 (s, 6H), 2.44-2.33 (m, 1H), 2.21 (m, 1H). 387 LC-MS¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] = 2.05-2.10 (m, 1H),2.19-2.24 M14): (m, 1H), 2.44 (s, 3H), 3.09 (s, 6H), Rt = 1.40 4.23-4.30(m, 2H), 5.26 (q, 1H), 6.81 min; (d, 1H), 6.94 (t, 1 H), 7.19 (t, 1H),7.39 m/z = 469 (d, 1H), 7.66 (t, 1H), 7.99 (s, 1H), 8.20 [M + H]+ (d,1H), 8.46 (d, 1H), 8.73 (s, 1H), 9.17 (d, 1H). 388 LC-MS ¹H-NMR (400MHz, DMSO-d6): δ (Method [ppm] = 2.04-2.08 (m, 1H), 2.16-2.23 M24): (m,4H), 2.41 (s, 3H), 3.05 (s, 6H), Rt = 1.27 4.22-4.30 (m, 2H), 5.26 (q,1H), 6.72 min; (s, 1H), 6.80 (s, 1H), 6.94 (t, 1H), 7.17 m/z = 458 (t,1H), 7.36 (d, 1H), 7.58-7.62 (m, 2H), [M + H]+ 7.13-7.17 (m, 1H), 8.56(s, 1H), 9.09 (d, 1H). 389 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method[ppm] = 2.06-2.09 (m, 1H), 2.20-2.22 M23): (m, 1H), 3.10 (s, 6H),4.25-4.29 (m, Rt = 1.65 2H), 5.26 (q, 1H), 6.81 (d, 1H), 6.96 min; (t,1H), 7.18 (t, 1H), 7.40 (d, 1H), 7.67 m/z = 455 (t, 1H), 7.97 (d, 1H),8.11 (d, 1H), 8.21 [M + H]+ (d, 1H), 8.53 (d, 1H), 8.75 (s, 1H), 9.18(d, 1H). 390 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm]: =2.08-2.09 (m, 1H), 2.20-2.23 M23): (m, 1H), 3.07 (s, 6H), 4.25-4.30 (m,Rt = 1.67 2H), 5.26 (q, 1H), 6.81 (d, 1H), 6.94 min; (t, 1H), 7.16-7.21(m, 2H), 7.40 (d, 1H), m/z = 464 7.61 (t, 1H), 7.81 (d, 1H), 8.10 (d,1H), [M + H]+ 8.33 (d, 1H), 8.70 (s, 1H), 9.15 (d, 1H). 391 LC-MS ¹H-NMR(400 MHz, DMSO-d6): δ (Method [ppm] = 2.05-2.10 (m, 1H), 2.18-2.24 M14):(m, 1H), 2.49 (s, 3H), 3.05 (s, 6H), Rt = 1.01 4.25-4.30 (m, 2H), 5.27(q, 1H), 6.80- min; 6.85 (m, 2H), 6.95 (t, 1H), 7.19 (t, 1H), m/z = 4447.39 (d, 1H), 7.57 (t, 1H), 7.66 (d, 1H), [M + H]+ 8.05 (d, 1H), 8.15(d, 1H), 8.67 (s, 1H), 9.14 (d, 1H). 399 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 9.02 (s, 1H), 8.29 (d, J = 5.1 Hz, 1H), L2):8.16 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 7.0 R_(t) = 2.31 Hz, 1H),7.63-7.54 (m, 1H), 7.33 (m, min; 2H), 7.21 (t, J = 7.7 Hz, 1H), 6.91 (m,m/z = 510 4H), 5.38 (q, J = 5.4 Hz, 1H), 4.40-4.31 [M + H]⁺. (m, 1H),4.26-4.16 (m, 1H), 3.88-3.79 (m, 4H), 3.59-3.51 (m, 4H), 3.13 (s, 6H),2.40 (m, 1H), 2.27-2.17 (m, 1H). 400 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.95 (s, 1H), 8.27-8.18 (m, 2H), 7.58 L2): (q, J= 4.5 Hz, 2H), 7.29 (d, J = 7.6 Hz, R_(t) = 2.86 1H), 7.20 (t, J = 7.2Hz, 2H), 6.92 (t, J = min; 7.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), m/z =489 6.78 (s, 1H), 5.37 (q, J = 5.4 Hz, 1H), [M + H]⁺. 4.33 (m, 1H),4.24-4.13 (m, 1H), 3.96 (s, 3H), 3.14 (s, 6H), 2.44-2.33 (m, 1H),2.25-2.14 (m, 1H). 401 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method8.96 (s, 1H), 8.41-8.25 (m, 2H), 8.18 L9): (d, J = 8.2 Hz, 1H), 7.59 (m,3H), 7.30 R_(t) = 3.59 (d, J = 7.6 Hz, 1H), 7.21 (m, 2H), 6.97- min;6.83 (m, 2H), 5.37 (q, J = 5.4 Hz, m/z = 510 1H), 4.34 (m, 1H),4.25-4.16 (m, 1H), [M + H]⁺. 3.77 (s, 3H), 3.13 (s, 6H), 2.39 (m, 1H),2.26-2.15 (m, 1H). 402 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method8.96 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), L2): 8.19 (d, J = 8.4 Hz, 1H),7.71 (d, J = 7.0 R_(t) = 2.25 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.50min; (s, 1H), 7.47 (d, J = 5.0 Hz, 1H), 7.30 m/z = 455 (d, J = 7.5 Hz,2H), 7.21 (t, J = 7.7 Hz, [M + H]⁺. 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.86(d, J = 8.2 Hz, 1H), 5.42-5.33 (m, 1H), 4.83 (s, 2H), 4.39-4.30 (m, 1H),4.25- 4.15 (m, 1H), 3.14 (s, 6H), 2.39 (m, 1H), 2.26-2.16 (m, 1H), 1.68(s, 1H). 403 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.91 (s,1H), 8.46 (s, 2H), 8.28 (d, J = L2): 8.5 Hz, 1H), 7.71 (d, J = 6.9 Hz,1H), R_(t) = 2.89 7.68-7.60 (m, 1H), 7.29 (d, J = 7.6 Hz, min; 1H),7.24-7.12 (m, 2H), 6.92 (t, J = m/z = 461 7.5 Hz, 1H), 6.86 (d, J = 8.2Hz, 1H), [M + H]⁺. 5.37 (q, J = 5.4 Hz, 1H), 4.34 (m, 1H), 4.24-4.14 (m,1H), 3.15 (s, 6H), 2.38 (m, 1H), 2.21 (m, 1H). 413 LC-MS ¹H-NMR (400MHz, Chloroform-d) δ (Method 8.94 (s, 1H), 8.24 (m, 1H), 7.72 (m, L2):1H), 7.65-7.57 (m, 1H), 7.30 (d, J = 7.6 R_(t) = 3.02 Hz, 1H), 7.25-7.17(m, 1H), 7.12 (s, min; 3H), 6.94 (t, J = 7.5 Hz, 1H), 6.87 (d, J = m/z =461 8.2 Hz, 1H), 5.38 (q, J = 5.4 Hz, 1H), [M + H]⁺. 4.35 (m, 1H), 4.21(m, 1H), 3.15 (s, 6H), 2.46-2.34 (m, 1H), 2.22 (m, 1H). 414 LC-MS ¹H-NMR(400 MHz, Chloroform-d) δ (Method 8.91 (s, 1H), 8.32-8.22 (m, 2H), 7.70L2): (d, J = 6.9 Hz, 1H), 7.66-7.58 (m, R_(t) = 2.97 1H), 7.36 (t, J =4.8 Hz, 1H), 7.30 (d, min; J = 7.5 Hz, 1H), 7.25-7.17 (m, 1H), 7.12 m/z= 477 (d, J = 7.4 Hz, 1H), 6.93 (t, J = 7.5 Hz, [M + H]⁺. 1H), 6.87 (d,J = 8.2 Hz, 1H), 5.37 (q, J = 5.3 Hz, 1H), 4.35 (m, 1H), 4.20 (m, 1H),3.15 (s, 6H), 2.39 (m, 1H), 2.21 (m, 1H). 415 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.88 (s, 1H), 8.47 (s, 1H), 8.25 (m, 1H), L2):7.65-7.56 (m, 2H), 7.36 (s, 1H), 7.29 R_(t) = 3.02 (d, J = 7.5 Hz, 1H),7.24-7.17 (m, min; 1H), 7.09 (d, J = 7.5 Hz, 1H), 6.92 (t, J = m/z = 4937.2 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), [M + H]⁺. 5.37 (q, J = 5.3 Hz,1H), 4.34 (m, 1H), 4.19 (m, 1H), 3.16 (s, 6H), 2.39 (m, 1H), 2.20 (m,1H). 416 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.98 (s, 1H),8.21 (m, 1H), 8.09-8.03 L2): (m, 1H), 7.67 (d, J = 6.3 Hz, 1H), 7.63-R_(t) = 3.14 7.55 (m, 1H), 7.30 (d, J = 7.6 Hz, min; 1H), 7.25-7.16 (m,2H), 6.96-6.83 m/z = 501 (m, 2H), 6.76 (d, J = 4.8 Hz, 1H), 5.37 [M +H]⁺. (q, J = 5.4 Hz, 1H), 5.27 (m, 1H), 4.34 (m, 1H), 4.19 (m, 1H), 3.13(s, 6H), 2.38 (m, 1H), 2.20 (m, 1H), 1.37 (d, J = 6.2 Hz, 6H). 429 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 10.23 (Method (s, 1H), 9.07 (d, J = 8.2 Hz,1H), 8.44 L2): (s, 1H), 7.69-7.55 (m, 3H), 7.49 (d, J = R_(t) = 3.0172.6 Hz, 1H), 7.36 (d, J = 7.5 Hz, 1H), min; 7.31 (d, J = 2.6 Hz, 1H),7.17 (t, J = 7.3 m/z = 508/ Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 6.79510/512 (d, J = 8.2 Hz, 1H), 5.24 (q, J = 5.9 Hz, [M + H]⁺. 1H),4.29-4.15 (m, 2H), 2.99 (s, 6H), 2.29-2.12 (m, 1H), 2.10-1.96 (m, 1H).433 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.1 Hz, 1H),8.50 (d, J = 0.8 Hz, L2): 1H), 8.29-8.21 (m, 1H), 7.95-7.87 R_(t) =3.189 (m, 1H), 7.66-7.58 (m, 2H), 7.52- min; 7.43 (m, 1H), 7.33 (d, J =7.7 Hz, 1H), m/z = 560 7.27-7.19 (m, 1H), 7.15 (t, J = 7.1 Hz, [M + H]⁺.1H), 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 5.27-5.17 (m,1H), 4.32- 4.16 (m, 2H), 3.07 (s, 6H), 2.24-2.12 (m, 1H), 2.08-1.96 (m,1H). 434 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.1 Hz,1H), 8.50 (d, J = 0.8 Hz, L2): 1H), 8.29-8.21 (m, 1H), 7.95-7.87 R_(t) =2.894 (m, 1H), 7.66-7.58 (m, 2H), 7.52- min; 7.43 (m, 1H), 7.33 (d, J =7.7 Hz, 1H), m/z = 510 7.27-7.19 (m, 1H), 7.15 (t, J = 7.1 Hz, [M + H]⁺.1H), 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 5.27-5.17 (m,1H), 4.32- 4.16 (m, 2H), 3.07 (s, 6H), 2.24-2.12 (m, 1H), 2.08-1.96 (m,1H). 435 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.2 Hz,1H), 8.53 (s, 1H), 8.32- L2): 8.23 (m, 1H), 7.96-7.84 (m, 2H), 7.80R_(t) = 2.808 (d, J = 8.3 Hz, 1H), 7.71-7.62 (m, 2H), min; 7.34 (d, J =7.4 Hz, 1H), 7.16 (t, 1H), m/z = 6.91 (t, 1H), 6.79 (d, 1H), 5.29-5.17483/485 (m, 1H), 4.33-4.17 (m, 2H), 3.08 (s, 6H), [M + H]⁺. 2.25-2.13(m, 1H), 2.10-1.95 (m, 1H). 436 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.08(Method (d, J = 8.2 Hz, 1H), 8.53 (s, 1H), 8.22 L2): (dd, J = 8.4, 1.4Hz, 1H), 7.66-7.60 (m, R_(t) = 2.711 1H), 7.59-7.53 (m, 1H), 7.37-7.26min; (m, 2H), 7.20-7.07 (m, 2H), 6.97 (d, J = m/z = 456 9.3 Hz, 1H),6.91 (t, J = 7.5, 1.0 Hz, [M + H]⁺. 1H), 6.79 (d, 1H), 5.28-5.19 (m,1H), 4.32-4.18 (m, 2H), 3.07 (s, 6H), 2.25- 2.13 (m, 1H), 2.1H.97 (m,1H), 1.90 (s, 3H). 437 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.08 (Method(d, J = 8.2 Hz, 1H), 8.54 (s, 1H), 8.22 L2): (dd, J = 8.0, 2.0 Hz, 1H),7.69-7.59 (m, R_(t) = 2.763 2H), 7.35 (d, J = 7.5 Hz, 1H), 7.28- min;7.07 (m, 4H), 6.91 (t, J = 7.5, 1.1 Hz, m/z = 456 1H), 6.79 (d, J = 8.2,0.9 Hz, 1H), 5.29- [M + H]⁺. 5.20 (m, 1H), 4.33-4.19 (m, 2H), 3.07 (s,6H), 2.34 (s, 3H), 2.26-2.13 (m, 1H), 2.11-1.99 (m, 1H). 441 LC-MS¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] = 2.03-2.09 (m, 1H),2.20-2.25 M22): (m, 1H), 3.27-3.29 (m, 4H), 3.86-3.88 Rt = 1.67 (m, 4H),4.21-4.29 (m, 2H), 5.26 min; (q, 1H), 6.80 (d, 1H), 6.94 (t, 1H), 7.18m/z = 540 (t, 1H), 7.24 (s, 1H), 7.38 (d, 1H), 7.70 [M + H]+ (t, 1H),7.79 (d, 1H), 8.28 (d, 1H), 8.67 (s, 1H), 9.19 (d, 1H). 442 LC-MS ¹H-NMR(400 MHz, DMSO-d6): δ (Method [ppm] = 2.07-2.08 (m, 1H), 2.21-2.23 M22):(m, 1H), 3.29-3.31 (m, 4H), 3.87-3.88 Rt = 1.46 (m, 4H), 4.22-4.31 (m,2H), 5.27 (q, min; 1H), 6.80 (d, 1H), 6.93 (t, 1H), 7.17- m/z = 506 7.20(m, 2H), 7.39 (d, 1H), 7.71 (t, 1H), [M + H]+ 7.81 (d, 1H), 7.92 (d,1H), 8.30 (d, 1H), 8.67 (s, 1H), 9.21 (d, 1H). 443 LC-MS ¹H-NMR (400MHz, DMSO-d6): δ (Method [ppm]: = 2.07-2.12 (m, 1H), 2.21-2.26 M22): (m,1H), 3.28-3.30 (m, 4H), 3.87-3.90 Rt = 1.84 (m, 4H), 4.23-4.31 (m, 2H),5.28 (q, min; 1H), 6.81 (d, 1H), 6.96 (t, 1H), 7.17- m/z = 506 7.21 (m,2H), 7.42 (d, 1H), 7.67 (t, 1H), [M + H]+ 7.83 (d, 1H), 8.14 (d, 1H),8.37 (d, 1H), 8.77 (s, 1H), 9.24 (d, 1H). 456 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.14 (Method (d, J = 8.2 Hz, 1H), 8.67 (s, 1H), 8.38 L2): (s,1H), 8.28 (d, J = 7.3 Hz, 1H), 8.13 Rt = 2.76 (d, J = 8.4 Hz, 1H),7.65-7.57 (m, min; 1H), 7.39 (d, J = 72 Hz, 1H), 7.22- m/z = 445 7.15(m, 1H), 6.95 (t, J = 7.4 Hz, 1H), [M + H]⁺. 6.81 (d, J = 8.2 Hz, 1H),5.30-5.22 (m, 1H), 4.34-4.21 (m, 2H), 3.07 (s, 6H), 2.68 (s, 3H),2.27-2.16 (m, 1H), 2.12- 2.01 (m, 1H). 457 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 9.05 (s, 1H), 8.03 (m, 2H), 7.58 (d, J = L2):1.5 Hz, 1H), 7.53 (m, 1H), 7.39 (d, J = R_(t) = 3.33 7.4 Hz, 1H), 7.32(d, J = 7.6 Hz, 1H), min; 7.26-7.17 (m, 2H), 6.95 (m, 1H), 6.88 m/z =464 (d, J = 8.2 Hz, 1H), 5.38 (q, J = 5.3 Hz, [M + H]⁺ 1H), 4.41-4.31(m, 1H), 4.22 (m, 1H), with Cl 3.11 (s, 6H), 2.45-2.34 (m, 1H), 2.23pattern. (m, 1H). 458 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method9.02 (s, 1H), 8.14-8.04 (m, 2H), 7.66- L2): 7.50 (m, 1H), 7.55 (m, 1H),7.48- R_(t) = 3.82 7.41 (m, 1H), 7.32 (d, δ = 7.7 Hz, 1H), min;7.26-7.17 (m, 2H), 6.95 (m, 1H), 6.91- m/z = 498 6.84 (m, 1H), 5.42-5.33(m, 1H), [M + H]⁺. 4.41-4.32 (m, 1H), 4.22 (m, 1H), 3.12 (s, 6H),2.46-2.34 (m, 1H), 2.28-2.16 (m, 1H), contains 2.696 (w/w) EtOAc and0.296 (w/w) DIP. 459 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 9.04(s, 1H), 8.00 (m, 2H), 7.56-7.49 L2): (m, 1H), 7.46 (d, J = 7.4 Hz, 1H),7.36- R_(t) = 3.26 7.29 (m, 2H), 7.25-7.17 (m, 1H), 6.95 min; (m, 1H),6.88 (d, J = 8.2 Hz, 1H), 6.52 m/z = 448 (m, 1H), 5.38 (q, J = 5.3 Hz,1H), 4.41- [M + H]⁺. 4.31 (m, 1H), 4.22 (m, 1H), 3.10 (s, 6H), 2.45-2.34(m, 1H), 2.28-2.17 (m, 1H). 460 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.86 (s, 1H), 8.65-8.59 (m, 2H), 8.27 L2): (m, 1H), 7.64 (m,1H), 7.55 (m, 1H), R_(t) = 2.96 7.28 (d, J = 7.8 Hz, 1H), 7.24-7.17 (m,min; 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.92 (m, m/z = 493 1H), 6.86 (d, J =8.3 Hz, 1H), 5.37 (q, [M + H]⁺ J = 5.3 Hz, 1H), 4.38-4.30 (m, 1H), 4.19with 2*Cl (m, 1H), 3.17 (s, 6H), 2.44-2.33 (m, pattern. 1H), 2.20 (m,1H). 461 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.19 (Method (t, 1H), 8.57(d, J = 2.4 Hz, 1H), 8.35- L2): 8.28 (m, 1H), 8.15-8.08 (m, 1H), 8.06-R_(t) = 3.774 8.00 (m, 1H), 7.74-7.65 (m, 3H), min; 7.35 (d, J = 7.7 Hz,1H), 7.16 (t, J = 7.6 m/z = 602 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H), 6.78[M + H] ⁺. (d, J = 8.1 Hz, 1H), 5.27-5.19 (m, 1H), 4.31-4.17 (m, 2H),3.94-3.85 (m, 4H), 3.37-3.22 (m, 4H, coinicdes with water signal),2.26-2.15 (m, 1H), 2.09-1.97 (m, 1H). 462 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.18 (Method (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.33- L2):8.25 (m, 1H), 7.73-7.66 (m, 2H), 7.62 R_(t) = 3.556 7.56 (m, 1H), 7.52(dd, J = 8.6, 2.5 Hz, min; 1H), 7.44 (bs, 1H), 7.37 (d, J = 7.3 Hz, m/z= 534/ 1H), 7.16 (t, 1H), 6.92 (t, J = 7.3 Hz, 536/538 1H), 6.79 (d, J =8.1 Hz, 1H), 5.29- [M + H] ⁺. 5.20 (m, 1H), 4.33-4.19 (m, 2H), 3.94-3.81 (m, 4H), 3.36-3.22 (m, 4H, coincides with water signal), 2.27-2.15(m, 1H), 2.11-1.99 (m, 1H). 463 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.19(Method (d, J = 8.2 Hz, 1H), 8.57 (d, J = 2.4 Hz, L2): 1H), 8.29 (dd, J= 7.8.2.1 Hz, 1H), 7.92 R_(t) = 3.464 (dt, J = 9.2.4.9 Hz, 1H),7.71-7.62 min; (m, 2H), 7.49 (td, J = 8.5, 2.3 Hz, 1H), m/z = 552 7.35(dd, J = 7.1, 2.8 Hz, 1H), 7.24 (ddd, [M + H] ⁺. J = 17.1, 9.3, 2.5 Hz,1H), 7.18-7.11 (m, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.1 Hz,1H), 5.28-5.20 (m, 1H), 4.32- 4.18 (m, 2H), 3.94-3.82 (m, 4H), 3.37-3.21 (m, 4H, coincides with water signal), 2.28-2.15 (m, 1H), 2.09-1.98(m, 1H). 464 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.18 (Method (d, J = 8.2Hz, 1H), 8.59 (s, 1H), 8.35- L2): 8.28 (m, 1H), 7.93 (dd, J = 8.3, 2.0Hz, R_(t) = 3.359 1H), 7.89 (s, 1H), 7.80 (d, J = 8.3 Hz, min; 1H), 7.72(d, J = 5.1 Hz, 2H), 7.36 (d, J = m/z = 7.2 Hz, 1H), 7.16 (t, 1H), 6.91(t, J = 525/527 7.3 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), [M + H] ⁺. 5.25(q, J = 5.8 Hz, 1H), 4.33-4.19 (m, 2H), 3.94-3.85 (m, 4H), 3.37-3.22 (m,4H, coincides with water signal), 2.27-2.16 (m, 1H), 2.10-1.99 (m, 1H).465 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.17 (Method (d, J = 8.0 Hz, 1H),8.58 (s, 1H), 8.26 L2): (dd, J = 8.4, 1.3 Hz, 1H), 7.72-7.64 (m, R_(t) =3.263 1H), 7.64-7.59 (m, 1H), 7.41 (d, J = min; 8.1 Hz, 1H), 7.36 (d, J= 7.3 Hz, 1H), m/z = 7.24 (dd, J = 8.3, 1.8 Hz, 1H), 7.21- 514/516 7.11(m, 2H), 6.91 (t, J = 7.3 Hz, 1H), [M + H] ⁺. 6.79 (d, J = 8.1 Hz, 1H),5.30-5.21 (m, 1H), 4.33-4.19 (m, 2H), 3.93-3.80 (m, 4H), 3.36-3.21 (m,4H, coincides with water signal), 2.33 (s, 3H), 2.27- 2.15 (m, 1H),2.10-1.99 (m, 1H). 466 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.16 (Method(d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 8.26 L2): (dd, J = 8.4.1.3 Hz, 1H),7.72-7.64 (m, R_(t) = 3.112 1H), 7.64-7.57 (m, 1H), 7.36 (d, J = min;7.2 Hz, 1H), 7.31 (dd, J = 8.3, 6.2 Hz, m/z = 498 1H), 7.20-7.09 (m,2H), 6.97 (d, J = [M + H] ⁺. 8.5 Hz, 1H), 6.91 (L 1H), 6.79 (d, J = 8.1Hz, 1H), 5.29-5.21 (m, 1H), 4.33- 4.19 (m, 2H), 3.93-3.82 (m, 4H), 3.36-3.22 (m, 4H, coincides with water peak), 2.27-2.16 (m, 1H), 2.10-2.00(m, 1H), 1.89 (s, 3H). 467 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.17(Method (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.27 L2): (dd, J = 7.4, 2.6Hz, 1H), 7.74-7.65 (m, R_(t) = 3.239 2H), 7.37 (d, J = 7.1 Hz, 1H),7.28- min; 7.22 (m, 1H), 7.22-7.10 (m, 3H), 6.92 m/z = 498 (t, J = 7.5,1.0 Hz, 1H), 6.80 (d, 1H), [M + H] ⁺. 5.30-5.22 (m, 1H), 4.33-4.19 (m,2H), 3.93-3.84 (m, 4H), 3.36-3.22 (m, 6H, coincides with water signal),2.34 (s, 3H), 2.27-2.16 (m, 1H), 2.11- 2.01 (m, 1H). 468 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 9.15 (Method (d, J = 8.1 Hz, 1H), 8.56 (s, 1H),8.23 L2): (dd, J = 8.5, 1.2 Hz, 1H), 7.66 (dd, J = R_(t) = 3.043 8.3,7.1 Hz, 1H), 7.56 (dd, J = 7.0, 1.2 min; Hz, 1H), 7.36 (d, J = 7.4 Hz,1H), 7.21- m/z = 494 7.12 (m, 2H), 7.12-7.05 (m, 1H), [M + H] ⁺.6.98-6.87 (m, 2H), 6.79 (d, J = 8.1 Hz, 1H), 5.31-5.20 (m, 1H),4.34-4.18 (m, 2H), 3.87 (s, 4H), 3.36-3.22 (m, 4H, coincides with watersignal), 2.29 (s, 3H), 2.26-2.15 (m, 1H), 2.1H.99 (m, 1H), 1.87 (d, J =6.7 Hz, 3H). 469 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.09 (Method (d, J =8.2 Hz, 1H), 8.53 (s, 1H), 8.30- L2): 8.20 (m, 1H), 7.65 (d, J = 5.1 Hz,2H), R_(t) = 2.944 7.59 (d, J = 8.6 Hz, 1H), 7.51 (dd, J = min; 8.6, 2.6Hz, 1H), 7.43 (bs, 1H), 7.34 (d, m/z = 492/ J = 7.4 Hz, 1H), 7.17 (t,1H), 6.91 (t, J = 494/496 7.3 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), [M + H]⁺. 5.27-5.19 (m, 1H), 4.32-4.18 (m, 2H), 3.07 (s, 6H), 2.26-2.13 (m,1H), 2.10- 1.96 (m, 1H). 470 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.09(Method (d, J = 8.1 Hz, 1H), 8.51 (s, 1H), 8.22 L9): (dd, J = 8.3, 1.4Hz, 1H), 7.67-7.55 (m, R_(t) = 2.815 2H), 7.40 (d, J = 8.0 Hz, 1H), 7.34(d, J = min; 7.5 Hz, 1H), 7.23 (d, J = 8.2, 1.8 Hz, m/z = 1H), 7.20-7.10(m, 2H), 6.91 (t, J = 7.4 472/474 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H),5.28- [M + H] ⁺. 5.19 (m, 1H), 4.32-4.19 (m, 2H), 3.07 (s, 6H), 2.33 (s,3H), 2.25-2.14 (m, 1H), 2.09-1.97 (m, 1H). 471 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.07 (Method (d, J = 8.2 Hz, 1H), 8.50 (s, 1H), 8.19 L2): (d,7.6 Hz, 1H), 7.61 (t, 1H), 7.52 (d, J = R_(t) = 2.770 6.1 Hz, 1H), 7.34(d, J = 7.5 Hz, 1H), min; 7.21-7.12 (m, 2H), 7.09 (d, J = 7.9 Hz, m/z =452 1H), 6.98-6.86 (m, 2H), 6.79 (d, J = [M + H] ⁺. 8.1 Hz, 1H),5.29-5.18 (m, 1H), 4.32- 4.17 (m, 2H), 3.06 (s, 6H), 2.29 (s, 3H),2.25-2.13 (m, 1H), 2.09-1.97 (m, 1H), 1.88 (d, J = 7.0 Hz, 3H). 472LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 9.03 (s, 1H), 8.15 (m,1H), 7.68 (m, L2): 1H), 7.57 (m, 1H), 7.38 (d, J = 7.5 Hz, R_(t) = 2.751H), 7.30 (d, J = 7.6 Hz, 1H), 7.24- min; 7.17 (m, 1H), 6.93 (m, 1H),6.87 (m, m/z = 485 1H), 6.55 (s, 2H), 5.38 (q, J = 5.4 Hz, [M + H]⁺.1H), 4.35 (m, 1H), 4.20 (m, 1H), 3.96 (s, 6H), 3.12 (s, 6H), 2.45-2.34(m, 1H), 2.21 (m, 1H). 473 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.97 (s, 1H), 8.20 (m, 1H), 7.68 (m, L2): 1H), 7.59 (m, 1H),7.40 (s, 1H), 7.34 (s, R_(t) = 2.76 1H), 7.31 (d, J = 7.7 Hz, 1H),7.24-7.16 min; (m, 2H), 6.94 (m, 1H), 6.90-6.84 (m, m/z = 473 1H), 5.38(q, J = 5.3 Hz, 1H), 4.40-4.31 [M + H]⁺ (m, 1H), 4.21 (m, 1H), 3.14 (s,6H), with Cl 2.61 (s, 3H), 2.46-2.34 (m, 1H), 2.22 pattern. (m, 1H). 474LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 9.00 (s, 1H), 8.17 (m,1H), 7.96 (d, J = L2): 5.1 Hz, 1H), 7.65 (m, 1H), 7.58 (m, 1H), R_(t) =2.54 7.42 (d, J = 7.5 Hz, 1H), 7.29 (d, J = 7.6 min; Hz, 1H), 7.24-7.16(m, 1H), 6.92 (m, m/z = 485 1H), 6.89-6.83 (m, 2H), 5.37 (q, J = [M +H]⁺. 5.4 Hz, 1H), 4.34 (m, 1H), 4.19 (m, 1H), 4.06 (s, 3H), 3.57 (s,3H), 3.13 (s, 6H), 2.45-2.33 (m, 1H), 2.21 (m, 1H). 475 LC-MS ¹H-NMR(400 MHz, Chloroform-d) δ (Method 8.94 (s, 1H), 8.25-8.18 (m, 1H), 8.13L2): (d, J = 5.1 Hz, 1H), 7.64-7.56 (m, R_(t) = 2.76 2H), 7.28 (d, J =7.7 Hz, 1H), 7.26- min; 7.15 (m, 2H), 6.95-6.89 (m, 2H), 6.86 m/z = 489(d, J = 8.2 Hz, 1H), 5.37 (q, J = 5.4 Hz, [M + H]⁺ 1H), 4.34 (m, 1H),4.19 (m, 1H), 4.08 with Cl (s, 3H), 3.14 (s, 6H), 2.44-2.32 (m, 1H),pattern. 2.20 (m, 1H). 476 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ(Method 8.88 (s, 1H), 8.36 (d, J = 4.8 Hz, 1H), L2): 8.25 (m, 1H),7.65-7.56 (m, 2H), 7.29 R_(t) = 2.91 (d, J = 7.7 Hz, 1H), 7.25 (d, J =4.8 Hz, min; 1H), 7.23-7.16 (m, 1H), 7.10 (d, J = 6.5 m/z = 493 Hz, 1H),6.92 (m, 1H), 6.89-6.83 (m, [M + H]⁺ 1H), 5.37 (q, J = 5.3 Hz, 1H),4.38- with 2*Cl 4.30 (m, 1H), 4.19 (m, 1H), 3.16 (s, pattern. 6H),2.44-2.33 (m, 1H), 2.20 (m, 1H). 480 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ(Method [ppm] = 2.05-2.06 (m, 1H), 2.16 (s, 3H), M22): 2.19-2.21 (m,1H), 2.42 (s, 3H), 3.26- Rt = 1.26 3.30 (m, 4H), 3.85-3.88 (m, 4H),4.24- min; 4.28 (m, 2H), 5.25 (q, 1H), 6.72 (d, 1H), m/z = 500 6.80 (d,1H), 6.94 (t, 1H), 7.18 (t, 1H), [M + H]+ 7.38 (d, 1H), 7.62-7.65 (m,2H), 8.20 (d, 1H), 8.63 (s, 1H), 9.16 (d, 1H). 491 LC-MS ¹H-NMR (400MHz, Chloroform-d) δ (Method 8.82 (d, J = 2.4 Hz, 1H), 8.29 (m, 1H),L2): 7.56 (m, 1H), 7.44 (t, J = 8.8 Hz, 1H), R_(t) = 3.75 7.34 (m, 2H),7.28 (s, 2H), 7.24 (m, min; 2H), 6.50 (d, J = 6.1 Hz, 1H), 5.72 (m, m/z= 536 1H), 3.94 (t, J = 3.9 Hz, 4H), 3.43 (m, [M + H]⁺. 4H), 3.10-2.90(m, 2H), 2.74 (m, 1H), 1.96 (m, 1H). 492 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.83 (d, J = 1.1 Hz, 1H), 8.29 (m, 1H), L2):7.56 (m, 1H), 7.44 (t, J = 8.8 Hz, 1H), R_(t) = 3.87 7.33 (m, 2H),7.25-7.08 (m, 4H), 6.65- min; 6.54 (m, 1H), 5.45-5.36 (m, 1H), m/z = 5504.12 (q, J = 7.2 Hz, 0H), 3.92 (m, 4H), [M + H]⁺. 3.43 (m, 4H),2.89-2.74 (m, 2H), 2.24- 2.11 (m, 1H), 2.09-1.98 (m, 1H), 1.97-1.77 (m,2H). 496 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.90 (d, J = 3.7Hz, 1H), 7.55-7.47 (m, L2): 2H), 7.36 (dd, J = 21.1, 7.6 Hz, 1H), 7.29Rt = 2.93 (d, J = 9.6 Hz, 2H), 7.24-7.18 (m, 2H), min; 6.99 (d, J = 8.1Hz, 1H), 6.92 (t, J = 7.5 m/z = Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 5.39564/566 (q, J = 5.5 Hz, 1H), 4.39-4.30 (m, [M + H]⁺; 1H), 4.24-4.16 (m,1H), 4.06 (s, 3H), Cl2 3.76 (d, J = 4.1 Hz, 4H), 3.36 (d, J = 4.3pattern. Hz, 4H), 2.49-2.32 (m, 1H), 2.28- 2.16 (m, 1H). 497 LC-MS¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.93 (s, 1H), 7.60 (d, J = 8.1Hz, 1H), L2): 7.42-7.35 (m, 2H), 7.35-7.28 (m, Rt = 2.92 2H), 7.21 (t, J= 7.1 Hz, 1H), 7.10 (t, J = min; 8.9 Hz, 1H), 6.99 (d, J = 8.2 Hz, 1H),m/z = 548 6.92 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.2 [M + H]⁺; Hz, 1H),5.39 (q, J = 5.2 Hz, 1H), 4.39- Cl pattern. 4.31 (m, 1H), 4.25-4.15 (m,1H), 4.06 (s, 3H), 3.76 (d, J = 11.3, 6.7, 5.6 Hz, 4H), 3.34 (t, J = 4.3Hz, 4H), 2.47- 2.34 (m, 1H), 2.27-2.15 (m, 1H). 498 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 9.18 (Method (d, J = 8.2 Hz, 1H), 8.56 (s, 1H), 7.65L2): (d, J = 2.3 Hz, 3H), 7.53 (dd, J = 13.3, R_(t) = 3.98 2.7 Hz, 2H),7.38 (d, J = 7.4 Hz, 1H), min; 7.17 (t, J = 7.2 Hz, 1H), 6.93 (t, J =7.5 m/z = Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 5.26 564/566 (q, J = 5.9Hz, 1H), 4.34-4.20 (m, [M + H]⁺. 2H), 3.98 (s, 3H), 3.88 (t, J = 4.0 Hz,4H), 3.31-3.20 (m, 4H), 2.28-2.16 (m, 1H), 2.12-2.01 (m, 1H). 499 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.22- (Method 9.11 (m, 1H), 8.45 (d, J = 1.6Hz, 1H), L2): 7.73-7.67 (m, 1H), 7.53 (d, J = 2.7 Hz, R_(t) = 3.61 1H),7.47-7.40 (m, 1H), 7.35 (d, J = min; 7.1 Hz, 3H), 7.16 (t, J = 7.6 Hz,1H), m/z = 6.91 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.2 564/566 Hz, 1H),5.25 (d, J = 6.2 Hz, 1H), 4.25 [M + H]⁺. (dt, J = 7.8, 4.6 Hz, 2H), 3.97(s, 3H), 3.88 (s, 4H), 3.30-3.19 (m, 4H), 2.26- 2.15 (m, 1H), 2.09-2.00(m, 1H). 500 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.17 (Method (d, J = 8.2Hz, 1H), 8.49 (s, 1H), 7.58- L2): 7.49 (m, 3H), 7.45 (d, J = 2.7 Hz,1H), R_(t) = 3.65 7.39-7.31 (m, 2H), 7.17 (t, J = 7.2 Hz, min; 1H), 6.92(t, J = 7.2 Hz, 1H), 6.79 (d, J = m/z = 8.1 Hz, 1H), 5.26 (q, J = 5.9Hz, 1H), 548/550 4.33-4.19 (m, 2H), 3.97 (s, 3H), 3.88 [M + H]⁺. (t, J =4.2 Hz, 4H), 3.31-3.21 (m, 4H), 2.29-2.15 (m, 1H), 2.11-2.00 (m, 1H).501 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.11 (Method (d, J = 8.2 Hz, 1H),8.51 (s, 1H), 7.64 L2): (s, 3H), 7.52-7.46 (m, 2H), 7.37 (d, J = R_(t) =3.42 7.5 Hz, 1H), 7.17 (t, J = 7.1 Hz, 1H), min; 6.93 (t, J = 7.4 Hz,1H), 6.80 (d, J = m/z = 8.1 Hz, 1H), 5.25 (q, J = 5.8 Hz, 1H), 522/5244.34-4.20 (m, 2H), 3.96 (s, 3H), 3.03 [M + H]⁺. (s, 6H), 2.26-2.15 (m,1H), 2.09-2.01 (m, 1H). 502 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.09(Method (dd, J = 8.0, 5.0 Hz, 1H), 8.40 (s, 1H), L2): 7.69 (dd, J = 8.0,1.4 Hz, 1H), 7.50 (d, J = R_(t) = 3.09 2.8 Hz, 1H), 7.47-7.40 (m, 1H),7.32 min; (dd, J = 11.9, 5.4 Hz, 3H), 7.16 (t, J = m/z = 7.2 Hz, 1H),6.90 (t, J = 7.4 Hz, 1H), 522/524 6.78 (d, J = 8.0 Hz, 1H), 5.23 (d, J =5.9 [M + H]⁺. Hz, 1H), 4.31-4.19 (m, 2H), 3.96 (s, 3H), 3.04 (s, 6H),2.25-2.13 (m, 1H), 2.06 (d, J = 15.1 Hz, 1H). 503 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.10 (Method (d, J = 8.2 Hz, 1H), 8.44 (s, 1H), 7.56- L2):7.48 (m, 3H), 7.42 (d, J = 2.8 Hz, 1H), R_(t) = 3.15 7.34 (t, J = 8.9Hz, 2H), 7.20-7.12 (m, min; 1H), 6.91 (t, J = 7.1 Hz, 1H), 6.79 (d, J =m/z = 506 8.0 Hz, 1H), 5.24 (q, J = 5.8 Hz, 1H), [M + H]⁺. 4.31-4.19 (m,2H), 3.96 (s, 3H), 3.04 (s, 6H), 2.25-2.14 (m, 1H), 2.09-1.98 (m, 1H).504 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 9.15 (s, 1H), 8.20(d, J = 7.4 Hz, 1H), L9): 7.59 (d, J = 8.1 Hz, 1H), 7.46 (d, J = 1.8R_(t) = 4.28 Hz, 2H), 7.37-7.29 (m, 2H), 7.21 (t, J = min; 7.2 Hz, 1H),6.90 (dd, J = 26.6, 8.1 Hz, m/z = 3H), 5.40 (q, J = 5.3 Hz, 1H), 4.40-522/524 4.31 (m, 1H), 4.26-4.16 (m, 1H), 4.04 [M + H]⁺. (s, 3H), 2.89(s, 6H), 2.44-2.33 (m, 1H), 2.27-2.16 (m, 1H). 505 LC-MS ¹H-NMR (400MHz, Chloroform-d) δ (Method 9.14 (d, J = 5.6 Hz, 1H), 8.33 (dd, J =L9): R_(t) = 21.9, 7.3 Hz, 1H), 7.55-7.47 (m, 2H), 4.00 min; 7.34-7.27(m, 2H), 7.21 (dd, J = 16.7, m/z = 8.0 Hz, 2H), 7.01-6.77 (m, 3H), 5.44-522/524 5.32 (m, 1H), 4.38-4.30 (m, 1H), 4.25- (Cl2 4.16 (m, 1H), 4.05(s, 3H), 2.89 (s, 6H), pattern; 2.37 (td, J = 9.7.4.7 Hz, 1H), 2.27-2.15[M + H]⁺. (m, 1H). 506 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method9.17 (s, 1H), 8.33 (d, J = 7.5 Hz, 1H), L2): 7.60 (d, J = 8.1 Hz, 1H),7.40 (dd, J = Rt = 2.74 6.2, 2.6 Hz, 1H), 7.32 (dd, J = 8.5, 4.4 min;Hz, 2H), 7.24-7.16 (m, 1H), 7.10 (t, m/z = J = 8.9 Hz, 1H), 7.01-6.84(m, 3H), 506/508 5.39 (q, 3 = 5.3 Hz, 1H), 4.39-4.30 [M + H]⁺. (m, 1H),4.25-4.16 (m, 1H), 4.04 (s, 3H), 2.88 (s, 6H), 2.43-2.32 (m, 1H),2.26-2.16 (m, 1H). 507 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method8.67 (s, 1H), 7.57-7.49 (m, 2H), 7.45 L2): (d, J = 1.8 Hz, 2H), 7.38 (t,J = 1.9 Hz, Rt = 3.29 1H), 7.30 (dd, J = 7.7, 1.6 Hz, 1H), 7.21 min; m/z= (dd, J = 15.4, 1.7 Hz, 1H), 6.98-6.90 526/528. (m, 1H), 6.86 (dd, J =8.3, 1.2 Hz, 1H), 6.24 (d, J = 7.7 Hz, 1H), 5.38 (q, J = 5.6 Hz, 1H),4.40-4.31 (m, 1H), 4.25-4.15 (m, 1H), 3.06 (s, 6H), 2.46-2.34 (m, 1H),2.27-2.16 (m, 1H). 508 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method8.64 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), L2): Rt = 7.51 (dd, J = 8.0, 1.7Hz, 1H), 7.44 (d, J = 3.06 min; 7.8 Hz, 1H), 7.29 (d, J = 7.4 Hz, 2H),m/z = 7.24-7.16 (m, 2H), 6.91 (t, J = 7.5 Hz, 526/528. 1H), 6.85 (dd, J= 8.3, 1.2 Hz, 1H), 6.31- 6.15 (m, 1H), 5.41-5.30 (m, 1H), 4.39- 4.26(m, 1H), 4.18 (t, 3 = 9.3 Hz, 1H), 3.06 (s, 6H), 2.44-2.33 (m, 1H), 225-2.14 (m, 1H). 509 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.66(s, 1H), 7.59-7.49 (m, 2H), 7.41- L2): Rt = 7.31 (m, 2H), 7.29 (dd, J =7.7, 1.7 Hz, 3.07 min; 1H), 7.24-7.16 (m, 1H), 7.11 (t, J = m/z = 8.9Hz, 1H), 6.96-6.89 (m, 1H), 6.85 510/512 (dd, J = 8.3, 1.2 Hz, 1H), 6.23(d, J = 7.6 (Cl2 Hz, 1H), 5.37 (q, J = 5.7 Hz, 1H), 4.39- pattern, 4.30(m, 1H), 4.23-4.14 (m, 1H), M + H)⁺. 3.06 (s, 6H), 2.44-2.33 (m, 1H),2.25- 2.15 (m, 1H). 510 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method9.23-9.11 (m, 1H), 8.65 (s, 1H), 8.54 L2): R_(t) = (s, 1H), 7.93 (s,1H), 7.73 (d, 1H), 3.828 min; 7.50-7.43 (m, 1H), 7.43-7.31 (m, 2H), m/z= 560/ 7.16 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.4 562/564 Hz, 1H), 6.79(d, J = 8.1 Hz, 1H), 5.28- [M + H] ⁺. 5.19 (m, 1H), 4.32-4.17 (m, 2H),3.11 (s, 6H), 2.25-2.14 (m, 1H), 2.09-1.97 (m, 1H). 511 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 9.18 (Method (d, J = 8.1 Hz, 1H), 8.68 (s, 1H),8.54 L2): R_(t) = (s, 1H), 8.03 (s, 1H), 7.62-7.53 (m, 3.897 min; 2H),7.41-7.32 (m, 2H), 7.17 (t, J = 7.5 m/z = Hz, 1H), 6.92 (t, J = 7.3 Hz,1H), 6.79 544/546 (d, J = 8.2 Hz, 1H), 5.24 (q, J = 5.6 Hz, [M + H] ⁺.1H), 4.33-4.17 (m, 2H), 3.11 (s, 6H), 2.26-2.14 (m, 1H), 2.11-1.98 (m,1H). 512 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.28 (Method (d, J = 8.1 Hz,1H), 8.85 (s, 1H), 8.53 L2): R_(t) = (s, 1H), 8.11 (s, 1H), 7.70 (s,3H), 7.40 4.340 min; (d, J = 7.3 Hz, 1H), 7.18 (t, J = 7.2 Hz, m/z =602/ 1H), 6.94 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 604/606 8.0 Hz, 1H),5.26 (q, J = 5.6 Hz, 1H), [M + H] ⁺. 4.35-4.17 (m, 2H), 3.95-3.83 (m,4H), 3.37-3.25 (m, 4H, coincides with water signal, 2.29-2.16 (m, 1H),2.14- 2.02 (m, 1H). 513 LC-MS ₁H-NMR (400 MHz, DMSO-d6) δ 9.31- (Method9.22 (m, 1H), 8.75 (d, J = 3.2 Hz, 1H), L2): R_(t) = 8.55 (s, 1H), 7.98(s, 1H), 7.74 (dd, J = 4.099 min; 8.0, 1.4 Hz, 1H), 7.52-7.44 (m, 1H),m/z = 602/ 7.44-7.33 (m, 2H), 7.17 (t, J = 7.6 Hz, 604/606 1H), 6.92 (t,J = 7.4 Hz, 1H), 6.79 (d, J = [M + H] ⁺. 8.1 Hz, 1H), 5.30-5.19 (m, 1H),4.34- 4.17 (m, 2H), 3.96-3.82 (m, 4H), 3.40-3.23 (m, 4H, coincides withwater signal), 2.29-2.15 (m, 1H), 2.12- 1.97 (m, 1H). 514 ¹H-NMR (400MHz, DMSO-d6) δ 9.27 (d, J = 8.1 Hz, 1H), 8.78 (s, 1H), 8.55 (s, 1H),8.08 (s, 1H), 7.65-7.54 (m, 2H), 7.44-7.33 (m, 2H), 7.17 (t, J = 7.2 Hz,1H), 6.93 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 5.26 (q, J =5.7 Hz, 1H), 4.34-4.16 (m, 2H), 3.95- 3.82 (m, 4H), 3.39-3.23 (m, 4H,coincides with water signal), 2.29-2.16 (m, 1H), 2.13-2.00 (m, 1H). 517LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 10.23 (Method (s, 1H), 9.17-9.07 (m,1H), 8.37 (d, J = L2): R_(t) = 2.2 Hz, 1H), 7.69 (dd, J = 8.0, 1.5 Hz,3.108 min; 1H), 7.53 (d, J = 2.7 Hz, 1H), 7.47- m/z = 550/ 7.38 (m, 1H),7.38-7.26 (m, 2H), 7.22- 552/554 7.11 (m, 2H), 6.91 (t, J = 7.5 Hz, 1H),[M + H] ⁺. 6.79 (d, J = 8.2 Hz, 1H), 5.24 (q, 1H), 4.34-4.18 (m, 2H),3.92-3.77 (m, 4H), 3.30-3.16 (m, 4H), 2.28-2.12 (m, 1H), 2.1H.95 (m,1H). 528 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 8.91 (Method (d, J = 8.3 Hz,1H), 8.29 (s, 1H), 7.93 L2): R_(t) = (d, J = 9.2 Hz, 1H), 7.50-7.41 (m,1H), 2.588 min; 7.35-7.29 (m, 2H), 7.29-7.19 (m, 1H), m/z = 7.19-7.08(m, 2H), 6.89 (t, J = 7.5 Hz, 491/493 1H), 6.77 (d, J = 8.0 Hz, 1H),5.47 (s, [M + H] ⁺. 2H), 5.25-5.15 (m, 1H), 4.30-4.17 (m, 2H), 2.99 (s,6H), 2.21-2.10 (m, 1H), 2.06-1.93 (m, 1H). 529 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 8.91 (Method (d, J = 8.2 Hz, 1H), 8.31 (s, 1H), 7.91 L2):R_(t) = (d, J = 9.2 Hz, 1H), 7.56 (t, J = 1.7 Hz, 2.722 min; 1H), 7.31(d, J = 7.5 Hz, 1H), 7.22 (d, m/z = 507/ J = 1.6 Hz, 2H), 7.19-7.07 (m,2H), 6.90 509/511 (t, J = 7.3 Hz, 1H), 6.78 (d, J = 8.1 Hz, [M + H] ⁺.1H), 5.48 (s, 2H), 5.20 (q, J = 6.0 Hz, 1H), 4.27-4.19 (m, 2H), 2.98 (s,6H), 2.21-2.10 (m, 1H), 2.05-1.95 (m, 1H). 530 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.93 (s, 1H), 7.59 (d, J = 8.2 Hz, 1H), L10): Rt= 7.44 (d, J = 1.9 Hz, 2H), 7.39-7.28 (m, 1.91 min; 4H), 7.26-7.16 (m,2H), 7.01-6.82 m/z = 564 (m, 3H), 5.51-5.20 (m, 1H), 4.48- [M + H] ⁺.4.28 (m, 1H), 4.28-4.12 (m, 1H), 4.05 (s, 3H), 3.76 (dt, J = 8.1.4.7 Hz,6H), 3.34 (t, J = 4.5 Hz, 6H), 2.55-2.33 (m, 1H), 2.33-2.14 (m, 1H). 531LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.63 (s, 1H), 7.62 (d, J= 7.8 Hz, 1H), L2): Rt = 7.54 (d, J = 7.8 Hz, 1H), 7.36 (dd, J = 3.76min; 7.8, 4.8 Hz, 2H), 7.30 (dd, J = 7.8, 1.6 m/z = Hz, 1H), 7.23-7.17(m, 1H), 7.15-7.07 552/554 (m, 1H), 6.93 (td, J = 7.5, 1.2 Hz, 1H), (Cl26.86 (dd, J = 8.1, 1.2 Hz, 1H), 6.20 pattern, (d, J = 7.6 Hz, 1H), 5.38(q, J = 5.6 Hz, [M + H] ⁺. 1H), 4.40-4.31 (m, 1H), 4.24-4.14 (m, 1H),4.15-3.75 (m, 4H), 3.43 (s, 4H), 2.46-2.35 (m, 1H). 532 LC-MS ¹H-NMR(400 MHz, Chloroform-d) δ (Method 8.61 (d, J = 3.9 Hz, 1H), 7.63 (d, J =7.8 L2): Rt = Hz, 1H), 7.52 (dd, J = 8.0, 1.6 Hz, 1H), 3.74 min; 7.47(d, J = 7.7 Hz, 1H), 7.33-7.27 (m, m/z = 2H), 7.20 (td, J = 7.6.1.7 Hz,2H), 6.96- 568/570 6.82 (m, 2H), 6.20 (t, J = 6.5 Hz, 1H), [M + H]⁺.5.42-5.33 (m, 1H), 4.39-4.31 (m, 1H), 4.23-4.13 (m, 1H), 3.99 (d, J =50.2 Hz, 4H), 3.44 (s, 4H), 2.46-2.34 (m, 1H), 2.26-2.16 (m, 1H). 533LC-MS ¹H-NMR (400 MHz, Chlofoform-d) δ (Method 8.65 (s, 1H), 7.60 (d, J= 7.8 Hz, 1H), L9): Rt = 7.53 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 1.9 4.38min; Hz, 2H), 7.39 (t, J = 1.9 Hz, 1H), 7.31 m/z = (dd, J = 7.6, 1.6 Hz,1H), 7.21 (dd, J = 568/570 15.6, 1.7 Hz, 1H), 6.98-6.91 (m, 1H), [M +H]⁺. 6.86 (dd, J = 8.3, 1.2 Hz, 1H), 6.20 (d, J = 7.6 Hz, 1H), 5.39 (q,J = 5.6 Hz, 1H), 4.41-4.33 (m, 1H), 4.25-4.16 (m, 1H), 3.95 (s, 4H),3.43 (s, 4H), 2.47-2.36 (m, 1H), 2.29-2.19 (m, 1H). 536 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 8.99 (Method (d, J = 8.3 Hz, 1H), 8.33 (s, 1H),7.98 L2): R_(t) = (d, J = 9.2 Hz, 1H), 7.50-7.43 (m, 2.60 min; 1H), 7.33(dt, J = 7.8, 4.6 Hz, 2H), m/z = 7.28-7.22 (m, 1H), 7.15 (t, J = 7.9 Hz,533/535 2H), 6.90 (t, J = 7.0 Hz, 1H), 6.78 (d, J = [M + H]⁺. 8.1 Hz,1H), 5.52 (s, 2H), 5.27-5.17 (m, 1H), 4.24 (dt, J = 8.6, 4.0 Hz, 2H),3.83 (s, 4H), 3.28-3.15 (m, 4H), 2.24- 2.12 (m, 1H), 2.06-1.95 (m, 1H).537 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.00 (Method (dd, J = 8.3, 2.3 Hz,1H), 8.31 (d, J = 2.0 L2): R_(t) = Hz, 1H), 7.97 (d, J = 9.2 Hz, 1H),7.64 2.67 min; (dd, J = 8.1, 1.4 Hz, 1H), 7.41 (td, J = m/z = 7.8, 5.9Hz, 1H), 7.32 (d, J = 7.3 Hz, 549/551 1H), 7.21-7.11 (m, 3H), 6.89 (t, J= [M + H]⁺. 7.4 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 5.37 (s, 2H), 5.21(q, J = 6.0 Hz, 1H), 4.25 (t, J = 8.5 Hz, 2H), 3.82 (s, 4H), 3.28-3.16(m, 4H), 2.23-2.12 (m, 1H), 2.06-1.95 (m, 1H). 538 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 8.98 (Method (d, J = 8.3 Hz, 1H), 8.36 (s, 1H), 7.96L2): R_(t) = (d, J = 9.2 Hz, 1H), 7.57 (t, J = 1.9 Hz, 2.72 min; 1H),7.33 (d, J = 7.3 Hz, 1H), 7.22 (d, J = m/z = 1.8 Hz, 2H), 7.18-7.11 (m,2H), 6.95- 549/551 6.87 (m, 1H), 6.78 (d, J = 8.1 Hz, 1H), [M + H]⁺.5.54 (s, 2H), 5.22 (q, J = 5.9 Hz, 1H), 4.31-4.18 (m, 2H), 3.82 (s, 4H),3.28- 3.14 (m, 4H), 2.19 (dq, J = 13.4, 4.8 Hz, 1H), 2.02 (dq, J = 10.4,3.7, 3.3 Hz, 1H). 551 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 8.92 (Method(dd, J = 8.4, 2.4 Hz, 1H), 8.27 (s, 1H), L2): 7.93 (d, J = 9.3 Hz, 1H),7.63 (dd, J = 2.66 min; 8.1, 1.7 Hz, 1H), 7.47-7.37 (m, 1H), 7.30 m/z =(dd, J = 7.6, 1.6 Hz, 1H), 7.23-7.07 (m, 507/509 3H), 6.88 (t, J = 7.4Hz, 1H), 6.77 (dd, J = [M + H]⁺. 8 3, 1.2 Hz, 1 H), 5.31 (d, J = 2.5 Hz,2H), 5.20 (q, J = 6.2 Hz, 1H), 4.24 (t, J = 5.9 Hz, 2H), 2.99 (s, 6H),2.23-2.10 (m, 1H), 2.06-1.92 (m, 1H). 559 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 10.37 (Method (s, 1H), 8.98 (d, J = 8.3 Hz, 1H), 8.41 L2):R_(t) = (s, 1H), 8.09 (d, J = 9.2 Hz, 1H), 7.48- 2.60 min; 7.40 (m, 1H),7.35-7.24 (m, 4H), 7.18- m/z = 492 7.12 (m, 1H), 6.90 (t, J = 7.3 Hz,1H), [M + H]⁺. 6.78 (d, J = 8.1 Hz, 1H), 5.21 (dd, J = 7.9, 5.1 Hz, 1H),4.30-4.18 (m, 2H), 3.03 (s, 6H), 2.22-2.12 (m, 1H), 2.06-1.96 (m, 1H).560 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 10.20 (Method (s, 1H), 8.98 (dd, J= 8.3, 2.4 Hz, 1H), L2): R_(t) = 8.37 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H),2.66 min; 7.61 (dd, J = 8.0, 1.5 Hz, 1H), 7.41- m/z = 7.27 (m, 3H),7.23-7.11 (m, 2H), 6.89 508/510 (t, J = 7.4 Hz, 1H), 6.77 (d, J = 8.1Hz, [M + H]⁺. 1H), 5.21 (q, J = 6.4 Hz, 1H), 4.25 (td, J = 9.4, 8.0, 5.5Hz, 2H), 3.03 (s, 6H), 2.22- 2.11 (m, 1H), 2.06-1.94 (m, 1H). 561 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 10.33 (Method (s, 1H), 8.98 (d, J = 8.2 Hz,1H), 8.44 L2): R_(t) = (s, 1H), 8.07 (d, J = 9.3 Hz, 1H), 7.54 (t, 2.74min; J = 2.0 Hz, 1H), 7.37-7.28 (m, 4H), m/z = 7.19-7.13 (m, 1H), 6.91(td, J = 7.5, 1.2 508/510 Hz, 1H), 6.78 (dd, J = 8.2, 1.1 Hz, 1H), [M +H]⁺. 5.26-5.18 (m, 1H), 4.30-4.19 (m, 2H), 3.02 (s, 6H), 2.23-2.12 (m,1H), 2.07-1.97 (m, 1H). 580 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method[ppm] = 2.04-2.09 (m, 1H), 2.17-2.30 M11): Rt = (m, 1H), 3.07 (s, 6H),4.22-4.32 (m 2H), 1.52 min; 5.21-5.26 (m, 1H), 6.79 (d, 1H), 7.33 m/z =570 (dd, 1H), 7.53 (d, 1H), 7.64-7.68 (m, [M + H]+ 4H), 7.81 (dd, 1H),8.25 (dd, 1H), 8.66 (s, 1H), 9.13 (d, 1H). 581 LC-MS ¹H-NMR (300 MHz,DMSO-d6): δ (Method [ppm] = 3.06 (s, 6H), 3.87 (dd, 1H), 4.05 M11): Rt =(dd, 1H), 4.75 (d, 2H), 5.18-5.21 (m, 1.29 min; 1H), 7.09-7.13 (m, 1H),7.25-7.30 (m, m/z = 4.92 2H), 7.47-7.50 (m, 1H), 7.62-7.67 [M + H]+ (m,4H), 7.80 (dd, 1H), 8.23 (dd, 1H), 8.62 (s, 1H), 9.11 (d, 1H), 584 LC-MS¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.90 (d, J = 2.5 Hz, 1H), 8.21(d, J = 9.3 L2): R_(t) = Hz, 1H), 7.47-7.40 (m, 1H), 7.40- 2.79 min;7.34 (m, 1H), 7.34-7.27 (m, 2H), m/z = 534 7.25-7.17 (m, 3H), 6.92 (t, J= 7.4 Hz, [M + H]⁺. 1H), 6.87 (d, J = 8.2 Hz, 1H), 5.46 (s, 1H), 5.36(dd, J = 7.6, 4.4 Hz, 1H), 4.38-4.30 (m, 1H), 4.22-4.14 (m, 1H), 3.84(q, J = 5.9 Hz, 4H), 3.40 (q, J = 4.4 Hz, 4H), 2.43-2.33 (m, 1H),2.27-2.16 (m, 1H). 609 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.19 (Method(dd, J = 8.1, 2.7 Hz, 1H), 8.68 (d, J = 1.9 L10): R_(t) = Hz, 1H), 8.44(d, J = 9.5 Hz, 1H), 7.77 3.98 min; (dt, J = 9.3, 1.6 Hz, 1H), 7.62-7.56(m, m/z = 602 1H), 7.49-7.34 (m, 3H), 7.20-7.14 [M + H]⁺. (m, 1H), 6.92(td, J = 7.5, 1.2 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.37-5.10 (m, 1H),4.32-4.18 (m, 2H), 3.88 (t, J = 4.8 Hz, 4H), 3.32-3.25 (m, 4H), 2.27-2.17 (m, 1H), 2.09-2.00 (m, 1H). 610 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ9.19 (Method (dd, J = 8.1, 4.2 Hz, 1H), 8.65 (d, J = 3.7 L10): R_(t) =Hz, 1H), 8.43 (d, J = 9.4 Hz, 1H), 7.76 4.00 min; (td, J = 8.8, 8.0, 1.6Hz, 2H), 7.48 (td, m/z = J = 7.9, 5.1 Hz, 1H), 7.38-7.29 (m, 2H),618/620 7.26-7.06 (m, 1H), 6.91 (tt, J = 7.5, 1.5 [M + H]⁺. Hz, 1H),6.79 (dd, J = 8.3, 1.2 Hz, 1H), 5.23 (d, J = 6.5 Hz, 1H), 4.31-4.19 (m,2H), 3.98-3.77 (m, 4H), 3.32-3.23 (m, 4H), 2.26-2.16 (m, 1H), 2.08-1.99(m, 1H). 611 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.19 (Method (d, J = 8.1Hz, 1H), 8.71 (s, 1H), 8.41 L10): R_(t) = (d, J = 9.5 Hz, 1H), 7.84-7.66(m, 2H), 4.20 min; 7.39 (dd, J = 19.0, 1.8 Hz, 3H), 7.22- m/z = 7.13 (m,1H), 6.96-6.88 (m, 1H), 6.79 618/620 (d, J = 8.1 Hz, 1H), 5.24 (q, J =6.0 Hz, [M + H]⁺. 1H), 4.32-4.19 (m, 2H), 3.98-3.71 (m, 4H), 3.32-3.22(m, 4H), 2.27-2.17 (m, 1H), 2.10-2.01 (m, 1H). 612 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 9.10 (Method (dd, J = 8.2, 2.8 Hz, 1H), 8.60 (s, 1H),L10): R_(t) = 8.41 (d, J = 9.5 Hz, 1H), 7.71 (dq, J = 3.67 min; 9.3, 1.5Hz, 1H), 7.61-7.55 (m, 1H), m/z = 560 7.47-7.33 (m, 3H), 7.16 (td, J =7.8, [M + H]⁺. 1.6 Hz, 1H), 6.91 (td, J = 7.5, 1.2 Hz, 1H), 6.79 (d, J =8.1 Hz, 1H), 5.22 (dt, J = 8.4, 4.3 Hz, 1H), 4.31-4.18 (m, 2H), 3.09 (s,6H), 2.25-2.14 (m, 1H), 2.09- 1.91 (m, 1H). 613 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.11 (Method (dd, J = 8.2, 3.8 Hz, 1H), 8.56 (d, J = 2.3L10): R_(t) = Hz, 1H), 8.40 (d, J = 9.4 Hz, 1H), 7.76- 3.60 min; 7.68(m, 2H), 7.47 (td, J = 7.9, 5.1 Hz, m/z = 1H), 7.36-7.28 (m, 2H),7.19-7.12 576/578 (m, 1H), 6.90 (tt, J = 7.3, 1.5 Hz, 1H), [M + H]⁺.6.78 (dd, J = 8.2, 1.2 Hz, 1H), 5.22 (d, J = 6.7 Hz, 1H), 4.31-4.17 (m,2H), 3.09 (s, 6H), 2.19 (td, J = 9.1, 8.7, 3.9 Hz, 1H), 2.08-1.96 (m,1H). 614 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.10 (Method (d, J = 8.2 Hz,1H), 8.62 (s, 1H), 8.38 L10): R_(t) = (d, J = 9.4 Hz, 1H), 7.70 (td, J =4.4, 2.2 3.82 min; Hz, 2H), 7.40 (d, J = 1.8 Hz, 2H), 7.35 m/z = (dd, J= 7.8, 1.6 Hz, 1H), 7.20-7.13 (m, 576/578 1H), 6.91 (t, J = 7.3 Hz, 1H),6.79 (d, J = [M + H]⁺. 8.2 Hz, 1H), 5.23 (q, J = 6.2 Hz, 1H), 4.31-4.19(m, 2H), 3.08 (s, 6H), 2.24- 2.14 (m, 1H), 2.08-1.99 (m, 1H). 615 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 10.24 (Method (s, 1H), 9.06 (dd, J = 8.3,2.9 Hz, 1H), L2): R_(t) = 8.43 (d, J = 2.5 Hz, 1H), 8.13 (d, J = 9.32.79 min; Hz, 1H), 7.62 (dd, J = 7.9, 1.6 Hz, 1H), m/z = 7.45-7.30 (m,3H), 7.24-7.11 (m, 550/552 211), 6.90 (t, J = 7.5 Hz, 1H), 6.78 (dd,[M + H]⁺. J = 8.3, 1.2 Hz, 1H), 5.22 (q, J = 6.3 Hz, 1H), 4.30-4.19 (m,2H), 3.85 (q, J = 4.8.3.8 Hz, 4H), 3.30-3.18 (m, 4H), 2.24-2.13 (m, 1H),2.09-1.96 (m, 1H). 616 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 10.36 (Method(s, 1H), 9.06 (d, J = 8.2 Hz, 1H), 8.51 L2): R_(t) = (s, 1H), 8.13 (d, J= 9.3 Hz, 1H), 7.55 2.92 min; (d, J = 2.1 Hz, 1H), 7.41-7.30 (m, m/z =4H), 6.92 (t, J = 7.4 Hz, 1H), 6.79 (d, 550/552 J = 8.1 Hz, 1H), 5.23(q, J = 5.9 Hz, 1H), [M + H]⁺. 4.32-4.19 (m, 2H), 4.04 (s, 1H), 3.90-3.79 (m, 4H), 3.24 (q, J = 5.3 Hz, 4H), 2.22-2.14 (m, 1H), 2.09-1.98 (m,1H). 617 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.16 (Method (d, J = 8.1 Hz,1H), 8.67 (s, 1H), 8.36 L9): R_(t) = (d, J = 8.6 Hz, 1H), 7.97 (d, J =8.7 Hz, 4.03 min; 1H), 7.77 (t, J = 1.9 Hz, 1H), 7.58 (s, m/z = 2H),7.35 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 517/519 7.7 Hz, 1H), 6.91 (t, J =7.5 Hz, 1H), [M + H]⁺. 6.79 (d, J = 8.2 Hz, 1H), 5.23 (q, J = 6.2 Hz,1H), 4.31-4.19 (m, 2H), 3.08 (s, 6H), 2.25-2.14 (m, 1H), 2.09-1.98 (m,1H). 618 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 10.18 (Method (s, 1H), 9.06(d, J = 8.2 Hz, 1H), 8.37 L2): R_(t) = (s, 1H), 7.55-7.44 (m, 3H),7.38-7.29 2.818 min; (m, 2H), 7.25 (d, J = 2.6 Hz, 1H), 7.16 m/z = 492/(t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.4 Hz, 494/496 1H), 6.79 (d, J = 8.0Hz, 1H), 5.24 (q, [M + H] ⁺. J = 5.9 Hz, 1H), 4.31-4.17 (m, 2H), 3.00(s, 6H), 2.26-2.13 (m, 1H), 2.09-1.95 (m, 1H). 619 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ 10.16 (Method (s, 1H), 9.10-9.00 (m, 1H), 8.33 (s, 1H),L2): R_(t) = 7.68 (d, 1H), 7.48 (d, J = 2.6 Hz, 1H), 2.836 min;7.47-7.36 (m, 1H), 7.36-7.27 (m, 2H), m/z = 508/ 7.20-7.10 (m, 2H), 6.90(t, J = 7.4 Hz, 510/512 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.29- [M + H] ⁺.5.16 (m, 1H), 4.31-4.15 (m, 2H), 3.00 (s, 6H), 2.17 (dd, J = 8.6, 4.2Hz, 1H), 2.01 (d, J = 13.7 Hz, 1H). 620 LC-MS ¹H-NMR (400 MHz,CD₃OD-d4): δ (Method [ppm] = 2.22-2.25 (m, 1H), 2.31-2.35 M24): Rt = (m,1H), 3.18 (s, 6H), 4.29-4.34 (m, 1.34 min; 1H), 4.38-4.43 (m, 1H), 5.36(t, 1H), m/z = 510 6.86-6.92 (m, 1H), 6.98-7.03 (m, 1H), [M + H]+ 7.17(d, 1H), 7.47 (t, 1H), 7.52 (d, 2H), 7.63 (dd, 1H), 7.71 (dd, 1H), 8.28(dd, 1H), 8.55 (s, 1H). 621 LC-MS ¹H-NMR (400 MHz, CD₃OD-d4): δ (Method[ppm]: = 2.20-2.26 (m, 1H), 2.29-2.35 M47): Rt = (m, 1H), 3.19 (s, 6H),4.33-4.39 (m, 2.86 min; 1H), 4.43-4.48 (m, 1H), 5.35 (t, 1H), m/z = 5607.33-7.36 (m, 2H), 7.47 (t, 1H), 7.52 [M + H]+ (d, 2H), 7.63 (dd, 1H),7.72 (dd, 1H), 8.29 (dd, 1H), 8.56 (s, 1H). 622 LC-MS ¹H-NMR (400 MHz,CD₃OD-d4): δ (Method [ppm]: = 2.16-2.21 (m, 1H), 2.27-2.32 M24): Rt =(m, 1H), 3.19 (s, 6H), 4.23-4.34 (m, 1.43 min; 2H), 5.32 (t, 1H), 6.80(d, 1H), 7.15 (dd, m/z = 526 1H), 7.37 (d, 1H), 7.47 (t, 1H), 7.52 (d,[M + H]+ 2H), 7.63 (dd, 1H), 7.72 (dd, 1H), 8.29 (dd, 1H), 8.56 (1 H,s). 623 LC-MS ¹H-NMR (300 MHz, DMSO-d6) δ (Method [ppm]: = 1.99-2.05(1H, m), 2.18-2.21 M47): Rt = (m, 1H), 3.06 (s, 6H), 4.19-4.27 (m, 2.86min; 2H), 5.19-5.24 (m, 1H), 6.84 (dd, 1H), m/z = 510 7.00-7.07 (m, 1H),7.17-7.22 (dd, 1H), [M + H]+ 7.64-7.68 (m, 4H), 7.81 (dd, 1H), 8.24 626LC-MS (dd, 1H), 8.68 (s, 1H), 9.13 (d, 1H). (Method ¹H-NMR (400 MHz,DMSO-d6) δ 10.25 L2): R_(t) = (s, 1H), 9.12 (d, J = 8.2 Hz, 1H), 8.403.240 min; (s, 1H), 7.58-7.49 (m, 2H), 7.47 (dd, J = m/z = 534/ 6.2, 2.7Hz, 1H), 7.40-7.29 (m, 2H), 536/538 7.27 (d, J = 2.6 Hz, 1H), 7.16 (t,1H), [M + H] ⁺. 6.92 (t, J = 7.5, 1.0 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H),5.26 (q, 1H), 4.33-4.18 (m, 2H), 3.93-3.77 (m, 4H), 3.30- 3.15 (m, 4H),2.28-2.14 (m, 1H), 2.12-1.97 (m, 1H). 627 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 10.41 (Method (s, 1H), 9.12 (d, J = 8.2 Hz, 1H), 8.46 L2):R_(t) = (s, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.60 (d, 3.529 min; J = 1.9Hz, 2H), 7.52 (d, J = 2.4 Hz, 1H), m/z = 550/ 7.37 (d, J = 7.2 Hz, 1H),7.32 (d, J = 2.6 552/554 Hz, 1H), 7.17 (t, 1H), 6.93 (t, 1H), 6.79 [M +H] ⁺. (d, J = 8.1 Hz, 1H), 5.25 (q, 1H), 4.33- 4.18 (m, 2H), 3.89-3.74(m, 4H), 3.27- 3.13 (m, 4H), 2.29-2.12 (m, 1H), 2.12-1.98 (m, 1H). 632LC-MS ¹H-NMR (300 MHz, DMSO-d6) δ (Method [ppm] = 2.07-2.11 (m, 1H),2.23-2.27 M30): Rt = (m, 1H), 3.06 (s, 6H), 4.31-4.45 (m, 1.65 min; 2H),5.28 (d, 1H), 6.94 (t, 1H), 7.35 (t m/z = 526 2H), 7.63-7.67 (m, 4H),7.81 (d, 1H), [M + H]+ 8.24 (d, 1H), 8.64 (s, 1H), 9.12 (d, 1H). 633LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm] = 2.06-2.10 (m, 1H),2.20-2.24 M14): Rt = (m, 1H), 3.06 (s, 6H), 4.31-4.44 (m, 2H), 1.43 min;5.26-5.31 (m, 1H), 6.88 (t, 1H), 7.40 (d, m/z = 570 1H), 7.48 (d, 1H),7.63-7.67 (m, 4H), [M + H]+ 7.80 (d, 1H), 8.24 (d, 1H), 8.64 (s, 1H),9.13 (d, 1H). 634 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] =2.06-2.10 (m, 1H), 2.20-2.24 M14): Rt = (m, 1H), 3.06 (s, 6H), 4.31-4.44(m, 2H), 1.43 min; 5.26-5.31 (m, 1H), 6.88 (t, 1H), 7.40 (d, m/z = 5701H), 7.48 (d, 1H), 7.63-7.67 (m, 4H), [M + H]+ 7.80 (d, 1H), 8.24 (d,1H), 8.64 (s, 1H), 9.13 (d, 1H). 642 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ9.24 (Method (dd, J = 8.1, 2.0 Hz, 1H), 8.74 (d, J = 2.7 L9): R_(t) =Hz, 1H), 8.42 (d, J = 8.8 Hz, 1H), 8.04 3.75 min; (d, J = 8.8 Hz, 1H),7.69-7.60 (m, m/z = 2H), 7.46 (td, J = 9.3, 7.0 Hz, 1H), 7.37 543/545(dd, J = 7.6.1.6 Hz, 1H), 7.20-7.14 (m, [M + H]⁺. 1H), 6.92 (td, J =7.5, 1.2 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.24 (dq, J = 10.3, 5.4 Hz,1H), 4.31-4.18 (m, 2H), 3.88 (t, J = 4.5 Hz, 4H), 3.29 (d, J = 4.8 Hz,4H), 2.28-2.15 (m, 1H), 2.05 (s, 1H). 651 LC-MS ¹H-NMR (400 MHz,Chloroform-d) δ (Method 8.80 (s, 1H), 8.11 (d, J = 7.4 Hz, 1H), L2):R_(t) = 7.78 (d, J = 7.5 Hz, 1H), 7.45-7.37 (m, 3.79 min; 2H), 7.31 (dd,J = 7.8, 1.7 Hz, 1H), 7.24- m/z = 534 7.18 (m, 1H), 7.15 (t, J = 8.8 Hz,1H), [M + H]⁺. 6.97-6.91 (m, 1H), 6.87 (dd, J = 8.1, 1.2 Hz, 1H), 6.21(d, J = 7.6 Hz, 1H), 5.45- 5.38 (m, 1H), 4.49 (s, 2H), 4.41-4.33 (m,1H), 4.24-4.15 (m, 1H), 3.86 (s, 2H), 3.68 (s, 2H), 3.17 (s, 2H), 2.51-2.37 (m, 1H), 2.30-2.22 (m, 1H). 652 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ9.24 (Method (d, J = 8.1 Hz, 1H), 8.76 (s, 1H), 8.39 L): R_(t) = (d, J =8.8 Hz, 1H), 8.01 (d, J = 8.8 Hz, 3.88 min; 1H), 7.78 (t, J = 1.9 Hz,1H), 7.59 (d, J = m/z = 1.9 Hz, 2H), 7.37 (dd, J = 7.8, 1.6 Hz, 559/6611H), 7.20-7.14 (m, 1H), 6.92 (td, J = [M + H]⁺. 7.5, 1.2 Hz, 1H), 6.79(dd, J = 8.1, 1.2 Hz, 1H), 5.28-5.21 (m, 1H), 4.32-4.18 (m, 2H), 3.88(t, J = 4.8 Hz, 4H), 3.31-3.24 (m, 4H), 2.26-2.18 (m, 1H), 2.09-2.01 (m,1H). 656 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 13.31 (Method (s, 1H), 9.19(d, J = 8.2 Hz, 1H), 8.69 L2): R_(t) = (s, 1H), 8.51 (dd, J = 7.4,1.4Hz, 1H), 2.697 min; 8.17 (dd, J = 8.5, 1.5 Hz, 1H), 7.65 (t, J = m/z =8.4, 7.4 Hz, 1H), 7.36 (dd, J = 7.9, 1.6 448/450 Hz, 1H), 7.32 (s, 1H),7.19 (ddd, J = [M + H]⁺. 8.7, 7.4, 1.7 Hz, 1H), 6.95 (t, J = 7.5, 1.2Hz, 1H), 6.82 (dd, J = 8.2, 1.1 Hz, 1H), 5.28 (q, J = 5.8 Hz, 1H),4.34-4.19 (m, 2H), 3.09 (s, 6H), 2.28-2.16 (m, 1H), 2.12-2.00 (m, 1H).657 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.77 (d, J = 4.0 Hz,1H), 8.12 (d, J = 7.4 L2): R_(t) = Hz, 1H), 7.70 (d, J = 7.3 Hz, 1H),7.57 3.83 min; (dd, J = 8.1, 1.5 Hz, 1H), 7.36-727 (m, m/z = 2H),7.24-7.17 (m, 2H), 6.93 (t, J = 559/561 7.3 Hz, 1H), 6.86 (dd, J = 8.3,1.1 Hz, [M + H]⁺. 1H), 6.21 (t, J = 6.6 Hz, 1H), 5.41 (t, J = 6.2 Hz,1H), 4.50 (s, 2H), 4.40-4.32 (m, 1H), 4.24-4.14 (m, 1H), 3.87 (s, 2H),3.69 (s, 2H), 3.31-3.03 (m, 2H), 2.42 (dd, J = 12.0, 6.7 Hz, 1H), 2.31-2.18 (m, 1H). 658 LC-MS ¹H-NMR (400 MHz, Chloroform-d) δ (Method 8.83(s, 1H), 8.10 (d, J = 7.4 Hz, 1H), L2): R_(t) = 7.78 (d, J = 7.5 Hz,1H), 7.47-7.39 (m, 3.86 min; 2H), 7.31 (dd, J = 7.9, 1.6 Hz, 1H), m/z =501 7.26-7.21 (m, 1H), 7.20-7.13 (m, 1H), [M + H]⁺. 6.99-6.92 (m, 1H),6.89 (dd, J = 8.3, 1.2 Hz, 1H), 6.23 (d, J = 7.7 Hz, 1H), 5.41 (q, J =5.6 Hz, 1H), 4.38 (dq, J = 10.3, 3.3 Hz, 1H), 4.26-4.18 (m, 1H), 3.08(s, 6H), 2.48-2.38 (m, 1H), 2.30-2.21 (m, 1H). 659 LC-MS ¹H-NMR (400MHz, Chloroform-d) δ (Method 8.78 (d, J = 1.3 Hz, 1H), 8.08 (d, J = 7.4L2): R_(t) = Hz, 1H), 7.67 (d, J = 7.4 Hz, 1H), 7.57 3.89 min; (dd, J =8.1, 1.5 Hz, 1H), 7.36-7.29 (m, m/z = 1H), 7.28 (s, 1H), 7.24-7.17 (m,2H), 517/519 6.96-6.89 (m, 1H), 6.86 (dd, J = 8.3, [M + H]⁺. 1.1 Hz,1H), 6.21 (t, J = 7.2 Hz, 1H), 5.38 (s, 1H), 4.39-4.31 (m, 1H), 4.23-4.14 (m, 1H), 3.07 (s, 6H), 2.47-2.35 (m, 1H), 2.26-2.16 (m, 1H). 660LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.26 (Method (d, J = 8.1 Hz, 1H), 8.87(s, 1H), 7.91- L2): R_(t) = 7.87 (m, 1H), 7.84-7.73 (m, 2H), 7.70- 3.65min; 7.57 (m, 1H), 7.35 (d, J = 7.8 Hz, m/z = 491 1H), 7.30-7.23 (m,1H), 7.19 (t, J = [M + H]⁺. 7.8 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.81(d, J = 8.2 Hz, 1H), 5.31-5.11 (m, 4H), 4.84-4.70 (m, 2H), 4.34-4.21 (m,2H), 2.25-2.15 (m, 1H), 2.08- 2.01 (m, 1H). 662 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.22 (Method (d, J = 8.2 Hz, 1H), 8.66 (s, 1H), 8.29 L2):R_(t) = (dd, J = 8.3, 1.7 Hz, 1H), 7.96-7.87 (m, 3.91 min; 2H),7.68-7.60 (m, 1H), 7.48-7.43 m/z = 561 (m, 1H), 7.31-7.25 (m, 1H), 7.21-[M + H]⁺. 7.14 (m, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.79 (dd, J =8.2, 1.1 Hz, 1H), 5.27 (q, J = 6.0 Hz, 1H), 4.34-4.19 (m, 2H), 2.23 (dp,J = 13.4, 4.3 Hz, 1H), 2.16-2.06 (m, 1H). 663 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.35 (Method (d, J = 8.0 Hz, 1H), 8.87 (s, 1H), 8.28 L2):R_(t) = (d, J = 7.6 Hz, 1H), 7.99 (d, J = 7.5 Hz, 4.04 min; 1H), 7.72(t, J = 1.9 Hz, 1H), 7.67 (d, J = m/z = 1.9 Hz, 2H), 7.45-7.38 (m, 1H),7.22- 559/561 7.15 (m, 1H), 6.94 (t, J = 7.4 Hz, 1H), [M + H]⁺.6.84-6.78 (m, 1H), 5.28 (q, J = 6.1 Hz, 1H), 4.34-4.17 (m, 4H), 3.78 (d,J = 10.9 Hz, 2H), 3.52 (s, 2H), 3.09 (s, 2H), 2.29-2.20 (m, 1H),2.14-2.05 (m, 1H). 664 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.28 (Method(d, J = 8.1 Hz, 1H), 8.86 (s, 1H), 8.26, L2): R_(t) = (d, J = 7.6 Hz,1H), 7.98 (d, J = 7.5 Hz, 4.11 min; 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.69(d, m/z = J = 2.0 Hz, 2H), 7.39 (d, J = 7.3 Hz, 1H), 517/519 7.22-7.15(m, 1H), 6.93 (t, J = 7.4 Hz, [M + H]⁺. 1H), 6.81 (d, J = 8.1 Hz, 1H),5.26 (q, J = 5.9 Hz, 1H), 4.31-4.22 (m, 2H), 2.91 (s, 6H), 2.27-2.15 (m,1H), 2.14-2.01 (m, 1H). 665 LC-MS ¹H-NMR (300 MHz, DMSO-d6): δ (Method[ppm] = 3.05 (s, 6H), 3.88 (dd, 1H), 4.04 M29): Rt = (dd, 1H), 4.79 (d,2H), 5.19-5.22 (m, 2.82 min; 1H), 7.11-7.17 (m, 1H), 7.36 (dd, 2H), m/z= 510 17.62-7.67 (m, 4H), 7.80 (dd, 1H), 8.23 [M + H]+ (dd, 1H), 8.63(s, 1H), 9.14 (d, 1H). 677 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.19(Method (dd, J = 8.3, 4.4 Hz, 1H), 8.80-8.67 (m, L2): R_(t) = 2H), 7.83(dd, J = 7.1, 1.2 Hz, 1H), 7.75 2.83 min; (dd, J = 8.6, 7.0 Hz, 1H),7.61 (dtd, J = m/z = 504 11.0, 5.9, 3.0 Hz, 1H), 7.35 (dd, J = 7.7, [M +H]⁺. 2.1 Hz, 1H), 7.22 (dp, J = 7.8, 2.4 Hz, 1H), 7.19-7.14 (m, 1H),6.92 (dd, J = 8.0, 6.8 Hz, 1H), 6.79 (dd, J = 8.2. 1.2 Hz, 1H), 5.29 (q,J = 6.4 Hz, 1H), 4.26 (td, J = 7.4, 7.0, 3.3 Hz, 2H), 3.99 (t, J = 8.9Hz, 1H), 3.31-3.22 (m, 4H), 3.02 (q, J = 8.3 Hz, 1H), 2.26-2.10 (m, 3H),2.09- 2.00 (m, 1H). 678 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 9.29- (Method9.14 (m, 1H), 8.75 (s, 1H), 8.53-8.19 L11): R_(t) = (m, 1H), 7.97-7.71(m, 2H), 7.61 (qd, J = 3.80 min 8.8, 3.3 Hz, 1H), 7.37 (d, J = 7.8 Hz,and 1H), 7.20 (dt, J = 27.0, 6.7 Hz, 2H), 6.93 3.84 min; (tt, J = 7.5,1.4 Hz, 1H), 6.79 (dd, J = m/z = 505 8.2, 12 Hz, 1H), 5.30 (q, J = 6.2Hz, 1H), [M + H]⁺. 4.34 (p, J = 8.8, 8.2 Hz, 1H), 4.27-4.13 (m, 3H),4.02 (dt, J = 29.8, 9.3 Hz, 1H), 3.87-3.56 (m, 1H), 3.25-3.15 (m, 1H),2.44-2.36 (m, 1H), 2.32-2.18 (m, 2H), 2.10-2.01 (m, 1H). 679 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ 9.14 (Method (d, J = 8.3 Hz, 1H), 8.72 (s,1H), 8.53 L2): R_(t) = (d, J = 8.5 Hz, 1H), 7.80 (dt, J = 15.6, 2.83min; 7.2 Hz, 2H), 7.61 (dq, J = 12.7, 8.0, 6.9 m/z = 532 Hz, 1H), 7.40(d, J = 7.6 Hz, 1H), 7.25- [M + H]⁺. 7.13 (m, 2H), 6.93 (t, J = 7.4 Hz,1H), 6.79 (d, J = 8.3 Hz, 1H), 5.31 (q, J = 6.5 Hz, 1H), 4.31-4.19 (m,2H), 2.94 (t, 7 = 11.7 Hz, 2H), 2.44 (d, J = 13.3 Hz, 3H), 2.25 (s, 4H),2.00 (dt, J = 23.1, 11.4 Hz, 3H), 1.77 (dd, J = 22.3, 12.8 Hz, 2H). 680LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method 13.95 (d, J = 7.7 Hz, 1H),9.35 (dd, J = L9): R_(t) = 8.2, 2.8 Hz, 1H), 8.67 (d, J = 3.3 Hz, 3.973min; 1H), 7.66 (dd, J = 8.0, 1.5 Hz, 1H), 7.55 m/z = (d, J = 7.9 Hz,1H), 7.44-7.34 (m, 2H), 550/552 7.30 (t, J = 7.4, 1.5 Hz, 1H), 7.17 (t,J = [M + H]⁺. 7.8 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 7.7Hz, 1H), 6.79 (dd, J = 8.2, 1.2 Hz, 1H), 5.25 (q, 1H), 4.35- 4.15 (m,2H), 3.85 (bs, 4H), 3.32 (bs, 4H, coincides with water signal), 2.30-2.15 (m, 1H), 2.13-1.99 (m, 1H). 681 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ14.16 (Method (s, 1H), 9.36 (d, J = 8.0 Hz, 1H), 8.79 L2): R_(t) = (d, J= 1.6 Hz, 1H), 7.75 (dd, J = 8.1, 1.6 4.067 min; Hz, 1H), 7.61-7.54 (m,3H), 7.41 (d, J = m/z = 7.8 Hz, 1H), 7.22-7.14 (m, 1H), 6.99- 550/5526.90 (m, 2H), 6.81 (dd, J = 8.2, 1.4 Hz, [M + H]⁺. 1H), 5.28 (q, J = 6.3Hz, 1H), 4.35- 4.18 (m, 2H), 3.85 (bs, 4H), 3.32 (bs, 4H, coincides withwater peak), 2.29- 2.17 (m, 1H), 2.14-2.02 (m, 1H). 682 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ 14.15, (Method (s, 1H), 9.30 (d, J = 8.0 Hz, 1H),8.67, L9): R_(t) = (d, J = 2.4 Hz, 1H), 7.65 (dd, J = 8.0, 1.6 4.036min; Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.44- m/z = 7.33 (m, 2H),7.33-7.26 (m, 1H), 508/510 7.17 (t, J = 7.6 Hz, 1H), 6.92 (dd, J = [M +H]⁺. 7.9, 2.9 Hz, 2H), 6.79 (dd, J = 8.3, 1.2 Hz, 1H), 5.24 (q, J = 6.0Hz, 1H), 4.31- 4.20 (m, 2H), 2.99 (s, 6H), 2.23-2.15 (m, 1H), 2.09-1.99(m, 1H). 683 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ 14.36 (Method (s, 1H),9.32 (d, J = 8.0 Hz, 1H), 8.79 L2): R_(t) = (s, 1H), 7.74 (d, J = 8.1Hz, 1H), 7.61- 3.335 min; 7.57 (m, 2H), 7.57-7.54 (m, 1H), m/z = 7.39(dd, J = 7.8.1.6 Hz, 1H), 7.18 (td, 505/510 J = 7.8, 7.3, 1.7 Hz, 1H),6.97-6.90 (m, [M + H]⁺. 2H), 6.81 (d, J = 8.2, 1.2 Hz, 1H), 5.26 (q, J =5.9 Hz, 1H), 4.33-4.18 (m, 2H), 2.99 (s, 6H), 2.27-2.16 (m, 1H), 2.13-2.02 (m, 1H). 689 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] =2.10-2.11 (m, 1H), 2.20-2.25 M48): R_(t) = (m, 1H), 3.20-3.25 (m, 4H),3.73-3.74 2.70 min; (m, 4H), 4.24-4.32 (m, 2H), 5.24 (q, m/z = 556 1H),6.81 (dd, 1H), 6.95 (t, 1H), 7.19 [M + H]+ (t, 1H), 7.39 (d, 1H),7.54-7.55 (m, 1H), 7.77-7.83 (m, 2H), 8.68 (s, 1H), 924 (d, 1H). 690LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm] = 2.05-2.10 (m, 1H),2.19-2.22 M29): Rt = (m, 1H), 2.97 (s, 6H), 4.23-4.29 (m, 2.91 min; 2H),5.22-5.24 (m, 1H), 6.81 (d, 1H), m/z = 514 6.94 (t, 1H), 7.17-7.21 (m,1H), 7.36 (d, [M + H]+ 1H), 7.52 (s, 1H), 7.72-7.75 (m, 2H), 8.59 (s,1H), 9.14 (d, 1H). 691 LC-MS ¹H-NMR (400 MHz, DMSO-d6): δ (Method [ppm]= 2.06-2.10 (m, 1H), 2.20-2.24 M48): Rt = (m, 1H), 3.27-3.32 (m, 4H),3.72-3.73 2.41 min; (m, 4H), 4.24-4.29 (m, 2H), 5.24 (q, m/z = 570 1H),6.81 (d, 1H), 6.95-6.97 (m, 1H), [M + H]+ 7.17-7.19 (m, 1H), 7.38-7.40(m, 1H), 7.70-7.78 (m, 4H), 8.65 (s, 1H), 9.24 (d, 1H). 692 LC-MS ¹H-NMR(400 MHz, CD₃OD-d4): δ (Method [ppm]: = 2.18-2.23 (m, 1H), 2.26-2.33M7): Rt = (m, 1H), 3.09 (d, 6H), 4.24-4.32 (m, 1.67 min; 2H), 5.30 (t,1H), 6.80-6.83 (m, 1H), m/z = 528 6.91-6.96 (m, 1H), 7.15-7.20 (m, 1H),[M + H]+ 7.33-7.36 (m, 1H), 7.50-7.58 (m, 4H), 8.50 (s, 1H). 693 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm] = 2.08-2.10 (m, 1H), 2.22-2.25M7): Rt = (m, l H), 3.20-3.32 (m, 4H), 3.70 (s, 1.71 min; 4H), 4.23-4.30(m, 2H), 5.24 (q, 1H), m/z = 570 6.81 (d, 1H), 6.94 (t, 1H), 7.19 (t,1H), [M + H]+ 7.39 (d, 1H), 7.57 (t, 1H), 7.63-7.65 (m, 1H), 7.78-7.85(m, 2H), 8.68 (s, 1H), 9.22 (t, 1H). 694 LC-MS ¹H-NMR (400 MHz,DMSO-d6): δ (Method [ppm] = 2.05-2.07 (m, 1H), 2.18-2.21 M7): Rt = (m,1H), 2.97 (s, 6H), 4.23-4.29 (m, 2H), 1.61 min; 5.21 (q, 1H), 6.81 (d,1H), 6.94 (t, 1H), m/z = 528 7.19 (t, 1H), 7.36 (d, 1H), 7.53-7.57 (m,[M + H]+ 1H), 7.63-7.64 (m, 1H), 7.72 (d, 1H), 7.81-7.84 (m, 1H), 8.58(s, 1H), 9.12- 9.14 (m, 1H). 374 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.149 (1.57), −0.008 (14.94), 0.008 L1): Rt = (13.32),0.146 (1.57), 2.038 (0.71), 2.103 1.38 min; (0.71), 2.179 (0.86), 2.214(1.11), 2.327 m/z = 602 (1.52), 2.366 (1.11), 2.523 (4.71), 2.670 [M +H]⁺ (1.62), 2.694 (1.01), 2.709 (1.16), 3.363 (2.08), 3.379 (1.47),3.405 (1.47), 3.436 (1.52), 3.462 (1.37), 3.490 (0.76), 4.120 (3.70),4.204 (0.96), 4.258 (1.67), 4.278 (1.92), 4.287 (1.97), 4.645 (0.96),5.243 (1.06), 5.285 (0.96), 6.798 (3.54), 6.818 (4.00), 6.861 (0.86),6.879 (1.77), 6.899 (1.06), 6.924 (0.91), 6.945 (1.82), 6.961 (1.11),7.160 (1.06), 7.178 (1.67), 7.188 (1.77), 7.285 (1.47), 7.304 (1.32),7.418 (1.57), 7.435 (1.52), 7.646 (14.89), 7.648 (16.00), 7.681 (0.86),7.717 (2.43), 7.735 (3.49), 7.756 (3.14), 7.868 (4.00), 7.886 (3.19),8.329 (1.87), 8.346 (2.53), 8.363 (1.57), 8.773 (6.43), 8.786 (6.73),8.962 (0.61), 9.262 (1.82), 9.282 (3.29), 9.303 (1.57). 375 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 2.028 (0.47), 2.050 (0.77), 2.065(0.73), L1): 2.132 (0.72), 2.145 (0.85), 2.160 (0.51), Rt = 0.93 3.644(16.00), 4.253 (1.62), 4.264 (2.51), min; MS 4.279 (1.47), 4.388 (1.53),4.404 (1.52), (ESIpos): 4.412 (1.50), 4.429 (1.52), 5.206 (0.44), m/z =536 5.221 (0.97), 5.240 (0.94), 5.255 (0.45), [M + H]⁺ 5.754 (0.63),6.782 (1.85), 6.802 (2.07), 6.891 (0.88), 6.910 (1.89), 6.928 (1.09),7.147 (0.94), 7.165 (1.54), 7.183 (0.71), 7.302 (1.62), 7.321 (1.48),7.575 (1.18), 7.594 (1.75), 7.616 (3.91), 7.626 (8.51), 7.631 (4.90),7.769 (2.16), 7.787 (1.79), 8.075 (0.67), 8.091 (1.40), 8.106 (0.67),8.160 (0.82), 8.351 (1.65), 8.372 (1.58), 8.522 (5.37), 9.077 (1.61),9.098 (1.57). 376 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ (Method [ppm]: 2.074(0.92), 2.081 (0.95), L1): 2.090 (1.23), 2.099 (1.37), 2.107 (1.62), Rt= 1.21 2.115 (1.60), 2.167 (1.52), 2.189 (1.28), min; MS 2.328 (0.53),2.671 (0.49), 4.258 (0.94), (ESIpos): 4.276 (2.38), 4.286 (2.24), 4.307(2.99), m/z = 449 4.317 (2.25), 4.325 (2.52), 4.345 (0.91), [M + H]⁺5.311 (1.02), 5.327 (2.32), 5.344 (2.34), 5.361 (1.07), 6.814 (4.66),6.835 (5.19), 6.877 (2.09), 6.894 (4.48), 6.912 (2.65), 7.163 (2.38),7.181 (3.70), 7.202 (1.79), 7.253 (3.98), 7.272 (3.65), 7.400 (3.14),7.405 (3.55), 7.420 (6.02), 7.424 (5.83), 7.457 (5.34), 7.477 (7.81),7.496 (3.47), 7.718 (5.20), 7.723 (5.42), 7.738 (4.66), 7.742 (4.46),7.755 (1.40), 7.772 (6.63), 7.781 (7.42), 7.789 (16.00), 7.798 (1.88),8.164 (3.15), 8.173 (2.91), 8.180 (2.79), 8.188 (2.77), 8.943 (7.32),8.948 (7.68), 9.208 (4.01), 9.217 (9.88), 9.222 (9.87), 9.228 (4.19).386 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (1.19),−0.008 (9.91), 0.146 L1): (1.21), 1.523 (9.91), 1.529 (10.20), 1.541 Rt= 1.36 (11.31), 1.552 (14.84), 1.572 (12.60), min; MS [2.009 (1.32),2.018 (1.45), 2.028 (1.53), (ESIpos): 2.045 (2.19), 2.052 (1.79), 2.072(1.11), m/z = 526 2.178 (1.87), 2.190 (1.79), 2.200 (1.69), [M + H]⁺2.327 (1.11), 2.366 (1.08), 2.669 (1.16), 2.709 (1.08), 3.848 (1.69),4.207 (1.05), 4.226 (3.16), 4.234 (2.79), 4.245 (4.93), 4.254 (5.27),4.270 (2.85), 4.289 (0.90), 5.243 (1.19), 5.258 (2.66), 5.276 (2.74),5.292 (1.13), 5.753 (6.70), 6.771 (5.67), 6.791 (6.19), 6.895 (2.45),6.914 (5.22), 6.933 (3.03), 7.141 (2.95), 7.159 (4.56), 7.176 (2.19),7.327 (2.64), 7.334 (2.87), 7.353 (2.53), 7.465 (3.58), 7.471 (3.85),7.489 (3.95), 7.495 (3.98), 7.736 (16.00), 7.745 (7.93), 7.752 (7.78),7.769 (1.27), 7.911 (8.30), 7.918 (8.20), 8.473 (3.87), 8.483 (3.43),8.489 (3.37), 8.498 (3.51), 8.669 (7.54), 8.679 (8.20), 9.119 (5.19),9.139 (5.06). 392 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (0.44), −0.008 (3.87), 0.008 L1): (3.75), 0.146 (0.44), 1.235(0.52), 2.012 Rt = 0.85 (0.57), 2.023 (0.75), 2.033 (0.65), 2.046 min;MS (1.16), 2.060 (1.08), 2.073 (1.84), 2.135 (ESIpos): (0.41), 2.149(1.12), 2.163 (1.23), 2.181 m/z = 522 (0.72), 2.199 (0.67), 2.327(0.42), 2.366 [M + H]⁺ (0.41), 2.523 (1.29), 2.670 (0.43), 2.710 (0.44),4.252 (2.47), 4.264 (4.03), 4.278 (2.39), 4.512 (0.46), 4.544 (1.08),4.577 (2.07), 4.606 (1.41), 4.637 (1.95), 4.647 (2.10), 4.661 (0.77),4.676 (0.74), 4.691 (0.69), 4.705 (0.72), 4.718 (0.44), 5.178 (0.62),5.193 (1.42), 5.212 (1.43), 5.226 (0.63), 5.411 (0.80), 5.557 (0.79),5.754 (4.87), 6.791 (2.68), 6.812 (2.97), 6.894 (1.29), 6.897 (1.35),6.915 (2.76), 6.931 (1.62), 6.934 (1.63), 7.150 (1.32), 7.154 (1.43),7.171 (2.22), 7.189 (1.09), 7.192 (1.09), 7.314 (2.35), 7.331 (2.17),7.472 (1.95), 7.490 (2.54), 7.493 (2.57), 7.511 (2.33), 7.614 (16.00),7.737 (3.27), 7.753 (2.63), 7.755 (2.75), 8.065 (2.69), 8.084 (2.39),8.181 (0.62), 8.488 (9.91), 9.045 (2.49), 9.065 (2.43). 393 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.46), 0.146 (0.50), 2.004(1.48), L1): 2.054 (1.02), 2.073 (1.42), 2.129 (0.86), Rt = 1.31 2.179(1.60), 2.192 (1.83), 2.203 (1.71), min; MS 2.214 (1.57), 2.327 (0.49),2.366 (0.54), (ESIpos): 2.669 (0.51), 2.710 (0.49), 3.015 (0.72), m/z =550 3.192 (1.52), 3.220 (1.63), 3.403 (0.84), [M + H]⁺ 3.429 (1.56),3.454 (1.45), 4.219 (0.48), 4.240 (1.51), 4.248 (1.25), 4.261 (2.24),4.270 (2.16), 4.287 (1.32), 4.306 (0.49), 4.909 (0.62), 5.030 (0.63),5.226 (0.65), 5.241 (1.44), 5.260 (1.43), 5.274 (0.66), 6.787 (2.64),6.807 (2.91), 6.912 (1.29), 6.931 (2.76), 6.950 (1.60), 7.156 (1.39),7.174 (2.28), 7.195 (1.06), 7.368 (2.41), 7.386 (2.21), 7.636 (16.00),7.682 (1.66), 7.701 (2.56), 7.721 (2.23), 7.826 (3.11), 7.844 (2.39),8.205 (2.59), 8.225 (2.30), 8.680 (8.42), 9.126 (2.54), 9.147 (2.47).394 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (3.00),0.008 (2.42), 2.044 (0.47), L1): 2.054 (0.42), 2.066 (0.71), 2.080(0.65), Rt = 1.00 2.169 (0.68), 2.183 (0.74), 2.202 (0.45), min; MS2.219 (0.41), 2.523 (0.83), 4.253 (1.55), (ESIpos): 4.266 (2.43), 4.279(1.48), 4.798 (2.52), m/z = 540 4.830 (5.19), 4.861 (2.27), 5.198(0.90), [M + H]⁺ 5.217 (0.92), 5.754 (0.78), 6.795 (1.66), 6.815 (1.81),6.902 (0.81), 6.918 (1.67), 6.937 (0.99), 7.155 (0.84), 7.159 (0.87),7.176 (1.38), 7.194 (0.66), 7.340 (1.43), 7.359 (1.33), 7.517 (1.16),7.535 (1.55), 7.538 (1.50), 7.556 (1.38), 7.620 (16.00), 7.779 (1.90),7.795 (1.64), 8.074 (1.60), 8.093 (1.48), 8.170 (0.52), 8.557 (5.90),9.136 (1.49), 9.156 (1.43). 396 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 0.008 (3.25), 1.618 (0.63), 1.631 (0.69), L1): 1.648 (0.77),1.909 (0.75), 1.922 (0.75), Rt = 1.18 1.930 (0.75), 1.943 (0.59), 2.327(0.50), min; MS 2.366 (0.50), 2.669 (0.53), 2.710 (0.51), (ESIpos):3.929 (0.61), 3.951 (1.23), 3.972 (0.85), m/z = 526 4.084 (0.88), 4.094(0.85), 4.102 (1.06), [M + H]⁺ 4.122 (0.64), 4.979 (0.55), 4.994 (1.22),5.013 (1.22), 5.028 (0.55), 6.717 (2.55), 6.737 (2.73), 6.787 (5.10),6.797 (4.07), 7.101 (0.99), 7.113 (1.39), 7.123 (1.52), 7.134 (1.07),7.144 (0.75), 7.421 (1.35), 7.469 (1.36), 7.580 (1.91), 7.601 (2.47),7.699 (16.00), 7.717 (2.39), 7.739 (1.49), 7.940 (2.48), 7.956 (2.12),8.753 (1.33), 8.764 (1.43), 8.806 (1.46), 8.817 (1.31), 8.867 (1.92),8.888 (1.86), 9.071 (6.62). 397 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (2.62), 0.844 (1.37), 0.859 (1.40), L1): 1.235 (0.54),1.800 (0.44), 2.047 (0.57), Rt = 1.05 2.523 (1.33), 2.670 (0.42), 4.167(0.67), min; MS 5.116 (0.76), 6.516 (0.46), 6.737 (2.19), (ESIpos):6.757 (2.43), 6.847 (1.09), 6.865 (0.73), m/z = 541 7.118 (1.00), 7.136(1.73), 7.154 (0.84), [M + H]⁺ 7.465 (0.93), 7.679 (16.00), 7.726(1.42), 7.747 (2.19), 7.765 (2.16), 7.869 (2.66), 7.890 (1.84), 7.917(2.54), 7.920 (2.39), 7.934 (2.12), 8.852 (1.93), 8.873 (1.95), 8.981(6.99). 398 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(2.48), 0.008 (2.72), 2.032 (0.71), L1): 2.039 (0.77), 2.052 (0.85),2.067 (1.16), Rt = 1.38 2.074 (0.99), 2.082 (0.73), 2.181 (0.77), min;MS 2.192 (1.10), 2.204 (1.13), 2.214 (1.15), (ESIpos): 2.251 (1.94),2.289 (2.48), 2.322 (1.97), m/z = 568 2.366 (0.45), 3.331 (1.13), 3.348(2.49), [M + H]⁺ 3.364 (4.98), 3.378 (4.86), 3.393 (2.42), 3.410 (0.88),4.210 (0.45), 4.217 (0.58), 4.238 (1.67), 4.245 (1.31), 4.259 (1.70),4.266 (2.15), 4.275 (1.76), 4.281 (1.44), 4.290 (1.42), 4.303 (0.49),4.309 (0.58), 5.228 (0.69), 5.243 (1.61), 5.262 (1.61), 5.276 (0.71),6.789 (3.07), 6.810 (3.40), 6.911 (1.52), 6.929 (3.14), 6.948 (1.84),7.156 (1.45), 7.159 (1.59), 7.176 (2.50), 7.194 (1.18), 7.198 (1.22),7.367 (2.67), 7.384 (2.44), 7.636 (5.96), 7.639 (16.00), 7.692 (2.00),7.713 (2.93), 7.731 (2.60), 7.847 (3.64), 7.864 (2.74), 8.262 (3.00),8.283 (2.65), 8.719 (10.73), 9.173 (2.85), 9.193 (2.80). 404 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.92, −0.008 (7.44),0.008 L1): (8.20), 0.146 (0.97), 1.759 (0.46), 1.783 Rt = 1.37 (1.32),1.806 (1.48), 1.830 (0.56), 2.045 min; MS (1.32), 2.071 (2.55), 2.096(1.99), 2.117 (ESIpos): (0.82), 2.179 (1.12), 2.191 (1.17), 2.201 m/z =503 (1.07), 2.270 (0.97), 2.295 (1.43), 2.322 [M + H]⁺ (2.50), 2.327(2.39), 2.347 (1.43), 2.366 (1.99), 2.523 (4.48), 2.605 (1.22), 2.626(2.60), 2.650 (2.45), 2.669 (2.29), 2.710 (1.58), 4.221 (0.61), 4.241(1.89), 4.249 (1.68), 4.260 (2.80), 4.269 (3.26), 4.283 (1.73), 4.301(0.61), 4.343 (0.41), 4.366 (1.02), 4.387 (1.63), 4.407 (0.97), 5.218(0.82), 5.233 (1.73), 5.252 (1.78), 5.266 (0.82), 6.781 (3.26), 6.801(3.62), 6.902 (1.68), 6.921 (3.46), 6.940 (2.09), 7.145 (1.68), 7.149(1.83), 7.166 (2.75), 7.187 (1.38), 7.342 (2.90), 7.359 (2.70), 7.630(8.76), 7.635 (16.00 7.645 (4.54J 7.649 (3.52), 7.654 (1.58), 7.684(2.39), 7.702 (3.26), 7.705 (3.11), 7.723 (3.11), 7.828 (3.87), 7.831(4.23), 7.846 (3.16), 7.849 (3.26), 8.185 (3.31), 8.203 (2.96), 8.747(11.87), 9.091 (3.11), 9.111 (3.01). 406 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method −0.008 (1.56), 0.008 (1.55), 1.529 (14.85), L1): 1.546(16.00), 1.555 (15.65), 1.573 Rt = 1.27 (14.94), 2.014 (0.47), 2.030(1.05), 2.038 min; MS (1.09), 2.048 (1.15), 2.056 (1.17), 2.065(ESIpos): (1.65), 2.072 (1.41), 2.080 (1.01), 2.089 m/z = 457 (0.68),2.171 (0.64), 2.181 (1.09), 2.193 [M + H]⁺ (1.44), 2.204 (1.41), 2.214(1.31), 2.228 (0.85), 2.236 (0.73), 2.248 (0.47), 3.830 (0.61), 3.848(1.53), 3.866 (2.04), 3.884 (1.51), 3.902 (0.60), 4.211 (0.53), 4.219(0.74), 4.239 (2.42), 4.247 (2.13), 4 258 (3.89), 4.267 (4.11), 4.282(2.22), 4.294 (0.55), 4.301 (0.71), 4.310 (0.46), 5.261 (1.00), 5.276(2.23), 5.296 (2.26), 5.310 (1.00), 6.781 (4.24), 6.801 (4.69), 6.910(2.06). 407 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149(0.46), 0.008 (4.67), 0.146 (0.51), L1): 1.530 (14.63), 1.548 (16.00),1.557 (15.62), Rt = 1.31 1.575 (14.69), 2.030 (1.04), 2.039 min; MS(1.13), 2.056 (1.22), 2.065 (1.66), 2.073 (ESIpos): (1.40), 2.081(1.00), 2.172 (0.67), 2.181 m/z = 507 (1.08), 2.193 (1.51), 2.205(1.40), 2.214 [M + H]⁺ (1.35), 2.229 (0.87), 2.248 (0.49), 2.327 (0.62),2.366 (0.53), 2.670 (0.66), 2.710 (0.58), 3.830 (0.62), 3.849 (1.53),3.866 (2.02), 3.885 (1.48), 3.903 (0.58), 4.217 (0.77), 4.237 (2.46),4.245 (2.06), 4.257 (3.81), 4.266 (3.83), 4.283 (2.19), 4.302 (0.77),5.262 (1.00), 5.276 (2.28), 5.296 (2.28), 5.310 (1.00), 6.781 (4.30),6.802 (4.74), 6.912 (2.10), 6.928 (4.43), 6.947 (2.61), 7.147 (2.22),7.150 (2.30), 7.167 (3.61), 7.185 (1.73), 7.189 (1.71), 7.344 (3.83),7.362 (3.72), 7.399 (2.33), 7.415 (2.61), 7.478 (0.44), 7.498 (0.67),7.561 (4.92), 7.579 (1.68), 7.598 (6.14), 7.608 (4.99), 7.615 (10.397.627 (1.57, 7.706 (0.73), 7.720 (3.01), 7.738 (4.46), 7.760 (4.03),7.815 (5.50), 7.830 (3.57), 8.429 (3.90), 8.448 (3.68), 8.717 (14.67,9.099 (3.86), 9.120 (3.81). 408 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.533 (14.48), 1.551 (16.00), 1.559 L1): (15.43), 1.577 (14.51),2.019 (1.10), 2.027 Rt = 1.26 (1.16), 2.037 (1.29), 2.043 (1.30), 2.053min; MS (1.77), 2.061 (1.48), 2.069 (1.06), 2.170 (ESIpos): (1.16),2.182 (1.57), 2.193 (1.49), 2.204 m/z = 509 (1.42), 2.216 (0.97), 2.669(0.41), 3.835 [M + H]⁺ (0.65), 3.852 (1.60), 3.870 (2.11), 3.888 (1.53),3.906 (0.64), 4.206 (0.81), 4.227 (2.52), 4.234 (2.16), 4.247 (3.95),4.256 (3.84), 4.273 (2.27), 4.292 (0.78), 5.247 (1.07), 5.261 (2.45),5.280 (2.43), 5295 (1.05), 6.773 (4.46), 6.793 (5.02), 6.899 (2.19),6.917 (4.73), 6.936 (2.74), 7.142 (2.33), 7.161 (3.88), 7.179 (1.81),7.338 (4.13), 7.357 (3.80), 7.499 (2.10), 7.518 (4.65), 7.538 (2.73),7.571 (0.56), 7.591 (1.20), 7.610 (0.68), 7.746 (2.26), 7.763 (5.20),7.774 (3.98), 7.784 (4.83), 7.806 (5.93), 7.826 (3.63), 7.848 (3.46),7.865 (1.75), 7.910 (0.66), 7.926 (0.75), 7.945 (0.64), 8.492 (3.95),8.513 (3.73), 8.684 (13.95), 9.126 (4.03), 9.147 (3.92). 409 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.49), −0.008 (4.30),0.008 L1): (4.43), 0.146 (0.48), 1.531 (14.92), 1.549 Rt = 1.24 (16.00),1.558 (15.65), 1.576 (14.94), min; MS 2.016 (1.06), 2.025 (1.12), 2.034(1.15), (ESIpos): 2.041 (1.17), 2.051 (1.63), 2.059 (1.41), m/z = 4752.067 (0.01), 2.163 (0.62), 2.172 (1.08), [M + H]⁺ 2.184 (1.45), 2.196(1.41), 2.205 (1.30), 2.219 (0.84), 2.226 (0.75), 2.239 (0.48), 2.327(0.49), 2.366 (0.70), 2.669 (0.59), 2.709 (0.71), 3.828 (0.60), 3.845(1.48), 3.863 (1.98), 3.881 (1.45), 3.899 (0.57), 4.202 (0.55), 4.210(0.79), 4.230 (2.42), 4.238 (2.09), 4.249 13.86), 4.258 (3.99), 4.275(2.18), 4.286 (0.59), 4.294 (0.75), 4.302 (0.48), 5.250 (0.99), 5.264(2.18), 5.284 (2.22), 5.298 (0.99), 6.774 (4.12), 6.792 (4.36), 6.795(4.54), 6.900 (2.03), 6.902 (2.11), 6.919 (4.30), 6.921 (4.32), 6.937(2.60), 6.940 (2.56), 7.140 (2.12), 7.144 (2.29), 7.161 (3.50), 7.179(1.70), 7.182 (1.70), 7.309 (2.18), 7.329 (5.82), 7.339 (3.97), 7.348(4.54), 7.357 (3.62), 7.384 (2.38), 7.388 (2.82), 7.399 (2.69), 7.403(3.70), 7.418 (1.65), 7.423 (1.54), 7.628 (1.94), 7.633 (2.05), 7.648(3.06), 7.666 (1.81), 7.670 (1.70), 7.730 (2.00), 7.748 (4.98), 7.768(6.90), 7.771 (6.96), 7.776 (6.74), 7.788 (2.22), 7.793 (1.39), 8.470(3.41), 8.475 (3.42), 8.491 (3.33), 8.495 (3.17), 8.692 (14.76), 9.114(3.73), 9.135 (3.70). 410 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (3.13), 0.008 (3.29), 0.146 (0.40), L1): 1.528 (14.85),1.546 (16.00), 1.555 Rt = 1.26 (15.61), 1.573 (15.00), 2.001 (0.49),2.016 min; MS (1.06), 2.025 (1.11), 2.035 (1.18), 2.042 (ESIpos):(1.17), 2.052 (1.64), 2.059 (1.39), 2.067 m/z = 475 (1.00), 2.163(0.65), 2.173 (1.07), 2.185 [M + H]⁺ (1.47), 2.197 (1.40), 2.207 (1.31),2.218 (0.85), 2.327 (0.48), 2.366 (0.42), 2.669 (0.53), 2.709 (0.46),3.821 (0.64), 3.839 (1.49), 3.857 (1.95), 3.874 (1.44), 3.892 (0.60),4.202 (0.56), 4.210 (0.78), 4 230 (2.43), 4.238 (2.08), 4.249 (3.91),4.259 (3.92), 4.275 (2.22), 4.294 (0.76), 5.251 (1.01), 5.265 (2.22),5.285 (2.26), 5.300 (0.99), 6.774 (4.47), 6.795 (4.89), 6.900 (2.08),6.903 (2.17), 6.921 (4.49), 6.937 (2.63), 6.940 (2.65), 7.141 (2.17),7.144 (2.30), 7.162 (3.63), 7.179 (1.71), 7.183 (1.71), 7.323 (3.21),7.338 (4.16), 7.345 (6.69), 7.355 (3.75), 7.368 (3.97), 7.485 (2.85),7.492 (4.04), 7.500 (2.96), 7.507 (4.05), 7.515 (2.58), 7.522 (2.10),7.525 (2.92), 7.533 (1.86), 7.536 (2.35), 7.544 (1.88), 7.547 (2.22),7.554 (1.51), 7.721 (2.43), 7.739 (4.57), 7.760 (4.71), 7.785 (5.80),7.799 (2.83), 8.463 (3.64), 8.466 (3.77), 8.484 (3.54), 8.487 (3.37),8.687 (15.55), 9.113 (3.86), 9.133 (3.75). 411 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.52), −0.008 (4.69), 0.008 L1):(4.82), 0.146 (0.52), 1.534 (14.70), 1.552 Rt = 1.31 (16.00), 1.560(15.73), 1.578 (14.85), min; MS 2.031 (1.01), 2.039 (1.07), 2.056(1.17), (ESIpos): 2.066 (1.67), 2.074 (1.42), 2.170 (0.64), m/z = 4912.191 (1.44), 2.203 (1.40), 2.213 (1.34), [M + H]⁺ 2.225 (0.87), 2.328(0.66), 2.366 (0.78), 2.670 (0.70), 2.710 (0.72), 3.840 (0.62), 3.856(1.50), 3.874 (2.00), 3.892 (1.50), 3.909 (0.58), 4.216 (0.76), 4.236(2.41), 4.245 (2.10), 4.256 (3.85), 4.265 (3.95), 4.282 (2.20), 4.300(0.76), 5.259 (0.97), 5.274 (2.22), 5.293 (2.27), 5.308 (1.01), 6.781(4.32), 6.801 (4.72), 6.910 (2.06), 6.928 (4.39), 6.945 (2.59), 7.145(2.20), 7.149 (2.33), 7.167 (3.62), 7.184 (1.71), 7.188 (1.69), 7.347(3.77), 7.364 (3.48), 7.511 (0.54), 7.694 (1.57), 7.713 (4.35), 7.732(6.71), 7.750 (4.76), 7.754 (5.35), 7.759 (5.37), 7.771 (4.57), 7.836(5.46), 7.852 (3.71), 7.874 (3.95), 7.897 (7.35), 8.441 (3.99), 8.461(3.67), 8.721 (15.16), 9.107 (3.85), 9.128 (3.77). 412 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: (Method 0.146 (0.43), 1.233 (0.49), 1.756 (0.67),L1): 1.768 (0.74), 1.784 (0.78), 2.002 (0.81), Rt = 1.12 2.015 (0.83),2.023 (0.78), 2.037 (0.56), min; MS 2.327 (0.67), 2.366 (0.58), 2.669(0.76), (ESIpos): 2.709 (0.61), 3.946 (0.74), 3.967 (1.32), m/z = 5423.988 (0.85), 4.134 (0.94), 4.152 (1.10), [M + H]⁺ 4.171 (0.72), 5.059(0.65), 5.074 (1.28), 5.093 (1.21), 5.107 (0.54), 6.729 (2.29), 6.749(2.44), 6.854 (0.94), 6.874 (2.31), 6.892 (1.77), 6.932 (2.42), 6.949(1.39), 7.094 (5.94), 7.108 (1.79), 7.130 (1.99), 7.147 (1.01), 7.685(16.00), 7.719 (1.55), 7.738 (2.20), 7.758 (2.11), 7.861 (2.62), 7.880(1.93), 7.921 (2.62), 7.938 (2.15), 8.272 (1.86), 8.864 (2.29), 8.884(2.13), 8.993 (6.79). 418 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (1.65), 0.008 (1.55), 1.529 (9.91), L1): 1.546 (10.68),1.556 (11.45), 1.574 Rt = 1.23 (10.97), 2.011 (0.79), 2.019 (0.83),2.329 min; MS (0.86), 2.036 (0.88), 2.046 (1.25), 2.054 (ESIpos):(1.05), 2.061 (0.78), 2.070 (0.55), 2.085 m/z = 475 (16.00), 2.158(0.47), 2.167 (0.82 2.180 [M + H]⁺ (1.09), 2.191 (1.07), 2.201 (0.98),2.212 (0.63), 2.523 (0.80), 3.816 (0.45), 3.833 (1.04), 3.851 (1.38),3.869 (1.03), 3.887 (0.42), 4.208 (0.56), 4.228 (1.84), 4.236 (1.62),4.247 (2.92), 4.255 (3.09), 4.271 (1.69), 4.283 (0.43), 4.290 (0.53),5.247 (0.74), 5.261 (1.64), 5.281 4.65), 5.295 (0.75), 6.771 (3.27),5.791 (3.58), 6.894 (1.53), 6.897 (1.53), 6.913 (3.26), 6.932 (1.99),6.934 (1.87), 7.137 (1.66), 7.141 (1.75), 7.158 (2.68), 7.175 (1.32),7.179 (1.28), 7.258 (1.26), 7.279 (1.22), 7.293 (1.89), 7.301 (1.38),7.315 (2.98), 7.323 (2.78), 7.331 (2.81), 7.336 (2.95), 7.344 (2.35),7.349 (2.44), 7.577 (1.76), 7.590 (1.90), 7.599 (1.75), 7.612 (1.58),7.682 (1.73), 7.686 (2.13), 7.700 (4.61), 7.703 (4.23), 7.717 (3.84),7.738 (3.71), 7.756 (1.81), 8.452 (2.70), 8.456 (2.79), 8.473 (2.60),8.477 (2.48), 8.660 (9.72), 9.115 (2.91), 9.136 (2.80). 419 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.50), −0.008 (4.19), 0.008L1): (4.14), 0.146 (0.48), 1.525 (14.78), 1.543 Rt = 1.30 (16.00), 1.552(15.64), 1.569 (14.85), min; MS 2.030 (1.00), 2.038 (1.03), 2.048(1.12), (ESIpos): 2.055 (1.12), 2.065 (1.63), 2.073 (1.39), m/z = 4752.081 (1.00), 2.171 (0.65), 2.180 (1.08), [M + H]⁺ 2.192 (1.46), 2.204(1.39), 2.214 (1.24), 2.228 (0.84), 2.327 (0.79), 2.366 (0.62), 2.669(0.84), 2.709 (0.67), 3.832 (0.62), 3.848 (1.48), 3.866 (2.03), 3.884(1.48), 3.902 (0.60), 4.210 (0.55), 4.219 (0.79), 4.239 (2.42), 4.247(2.06), 4.258 (3.87), 4.267 (3.99), 4.283 (2.18), 4.302 (0.72), 4.311(0.50), 5.260 (0.96), 5.275 (2.20), 5.294 (2.22), 5.309 (0.98), 6.781(4.28), 6.802 (4.71), 6.911 (2.01), 6.913 (2.08), 6.932 (4.35), 6.948(2.63), 6.951 (2.58), 7.147 (2.13), 7.151 (2.32), 7.169 (3.54), 7.186(1.70), 7.190 (1.75), 7.350 (3.71), 7.368 (3.44), 7.419 (3.16), 7.423(2.92), 7.444 (3.09), 7.447 (3.04), 7.457 (2.15), 7.462 (3.32), 7.467(2.25), 7.479 (1.87), 7.484 (3.52), 7.489 (2.87), 7.496 (5.60), 7.500(7.01), 7.624 (0.55), 7.717 (2.82), 7.735 (4.69), 7.756 (4.26), 7.838(5.41), 7.854 (3.78), 7.856 (3.73), 8.442 (3.97), 8.461 (3.61), 8.753(15.50 9.106 (3.90), 9.126 (3.80). 420 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (3.45), 0.008 (3.55), 0.146 (0.41), L1): 1.529(9.38), 1.539 (9.80), 1.547 (11.02), Rt = 1.27 1.559 (16.00), 1.578(11.91), 1.581 min; MS (11.87), 2.011 (1.20), 2.030 (1.39), 2.039(ESIpos): (1.60), 2.046 (1.79), 2.054 (1.43), 2.085 m/z = 525 (5.81),2.174 (1.52), 2.186 (1.56), 2.196 [M + H]⁺ (1.37), 2.327 (0.68), 2.366(0.75), 2.669 (0.68), 2.710 (0.73), 3.848 (1.31), 3.865 (1.68), 3.878(1.31), 4.199 (0.71), 4.219 (1.78), 4.227 (2.57), 4.241 (3.61), 4.250(4.05), 4.267 (2.68), 4.285 (0.85), 5.257 (2.24), 5.271 (2.20), 5.754(2.22), 6.767 (5.06), 6.788 (5.62), 6.888 (1.37), 6.892 (1.52), 6.906(2.91), 6.911 (3.15), 6.925 (1.81), 6.929 (1.89), 7.135 (2.64), 7.155(4.03), 7.174 (2.05), 7.319 (2.22), 7.337 (4.15), 7.354 (2.18), 7.424(0.50), 7.440 (0.83), 7.444 (0.87), 7.458 (0.42), 7.475 (0.42), 7.487(0.77), 7.505 (0.62), 7.609 (0.89), 7.627 (2.80), 7.640 (3.51), 7.646(3.20), 7.658 (5.83), 7.677 (3.53), 7.680 (3.53), 7.700 (1.81), 7.706(2.86), 7.709 (3.38), 7.723 (7.68), 7.727 (7.16), 7.736 (5.71), 7.757(5.40), 7.775 (2.37), 7.894 (0.44), 7.916 (4.48), 7.921 (4.48), 7.935(3.88), 7.940 (3.80), 8.475 (4.00), 8.479 (4.25), 8.496 (3.88), 8.500(3.84), 8.649 (8.55), 8.658 (9.36), 9.107 (2.39), 9.126 (3.82), 9.145(2.35). 421 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(0.74), 0.008 (0.66), 1.398 L1): (16.00), 1.531 (2.32), 1.549 (2.57),1.558 Rt = 1.22 (3.55), 1.576 (3.28), 2.044 (0.42), 3.853 min; MS(0.41), 4.226 (0.60), 4.235 (0.52), 4.245 (ESIpos): (0.96), 4.254(1.03), 4.270 (0.56), 5.259 m/z = 475 (0.53), 5.278 (0.54), 6.770(1.05), 6.790 [M + H]⁺ (1.17), 6.894 (0.43), 6.913 (0.95), 6.931 (0.55),7.136 (0.49), 7.139 (0.53), 7.157 (0.86), 7.175 (0.41), 7.178 (0.42),7.223 (0.50), 7.329 (0.63), 7.348 (0.59), 7.451 (1.08), 7.460 (1.29),7.472 (1.04), 7.479 (1.04), 7.685 (0.58), 7.688 (0.73), 7.702 (1.46),7.706 (1.42), 7.723 (1.24), 7.744 (1.24), 7.762 (0.62), 8.461 (0.89),8.464 (0.98), 8.482 (0.88), 8.485 (0.89), 8.653 (1.41), 9.113 (0.66),9.133 (0.64). 422 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (2.40), 0.008 (2.26), 1.141 (0.70), L1): 1.520 (7.81), 1.537(8.37), 1.547 (8.11), Rt = 1.26 1.564 (7.78), 2.023 (0.54), 2.031(0.58), min; MS 2.048 (0.63), 2.058 (0.85), 2.066 (0.74), (ESIpos):2.075 (0.59), 2.085 (6.90), 2.161 (16.00), m/z = 457 2.177 (0.76), 2.189(0.78), 2.201 (0.76), [M + H]⁺ 2.211 (0.70), 2.327 (0.45), 2.386 (0.52),2.395 (0.44), 2.416 (12.94), 2.670 (0.45), 3.822 (0.75), 3.841 (1.02),3.858 (0.72), 4.238 (1.26), 4.246 (1.09), 4.257 (2.03), 4.265 (2.14),4.282 (1.14), 5.259 (0.50), 5.273 (1.16), 5.293 (1.14), 5.307 (0.53),5.754 (0.60), 6.710 (3.80), 6.712 (3.83), 6.779 (2.31), 6.799 (2.52),6.911 (1.13), 6.927 (2.33), 6.946 (1.40), 7.145 (1.16), 7.149 (1.23),7.167 (1.85), 7.184 (0.91), 7.341 (1.95), 7.359 (1.78), 7.624 (1.06),7.628 (1.41), 7.642 (3.30), 7.646 (3.02), 7.655 (2.78), 7.676 (2.61),7.694 (1.18), 8.342 (1.79), 8.346 (1.89), 8.363 (1.74), 8.367 (1.66),8.686 (8.47), 9.079 (1.98), 9.100 (1.92). 423 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 1.141 (0.76), 1.356 (1.34), 1.519 (14.63),L1): 1.537 (16.00), 1.546 (15.53), 1.564 Rt = 1.35 (14.65), 2.023(1.05), 2.031 (1.09), 2.049 min; MS (1.27), 2.058 (1.67), 2.066 (1.49),2.085 (ESIpos): (11.52), 2.183 (1.31), 2.191 (1.53), 2.203 m/z = 497(1.48), 2.212 (1.37), 2.327 (0.60), 2.366 [M + H]⁺ (0.65), 2.670 (0.66),2.709 (0.66), 3.811 (0.65), 3.829 (1.53), 3.847 (2.05), 3.865 (1.54),3.881 (0.61), 4.215 (0.80), 4.235 (2.49), 4.243 (2.19), 4.255 (3.96),4.264 (3.93), 4.281 (2.31), 4.300 (0.76), 5.257 (1.04), 5.273 (2.31),5.292 (2.38), 5.306 (1.02), 5.754 (1.15), 6.779 (4.42), 6.799 (4.85),6.912 (2.14), 6.930 (4.56), 6.947 (2.64), 7.149 (2.39), 7.167 (3.78),7.188 (1.87), 7.231 (13.75), 7.346 (3.92), 7.364 (3.67), 7.716 (2.56),7.734 (4.37), 7.755 (4.14), 7.800 (5.63), 7.815 (3.43), 8.454 (3.95),8.473 (3.67), 8.737 (14.24), 9.105 (3.82), 9.125 (3.71). 424 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.62), 0.146 (0.58),2.082 (0.85), L1): 2.092 (0.94), 2.118 (1.45), 2.126 (1.23), Rt = 0.832.220 (1.28), 2.232 (1.23), 2.242 (1.10), min; MS 2.328 (0.69), 2.366(0.74), 2.670 (0.75), (ESIpos): 2.710 (0.77), 3.046 (2.57), 3.168(0.82), m/z = 492 3.426 (3.56), 3.443 (4.68), 4.227 (0.88), [M + H]⁺4.247 (2.21), 4.256 (1.97), 4.267 (3.31), 4.275 (3.45), 4.292 (1.93),4.310 (0.72), 5.298 (1.79), 5.314 (1.79), 6.790 (3.71), 6.811 (4.03),6.913 (1.81), 6.931 (3.79), 6.949 (2.21), 7.158 (1.97), 7.176 (3.10),7.196 (1.57), 7.376 (3.26), 7.394 (2.97), 7.646 (8.78), 7.650 (16.00),7.658 (5.74), 7.662 (4.49), 7.772 (1.84), 7.790 (3.18), 7.811 (2.48),7.898 (4.35), 7.915 (3.20), 8.337 (0.98), 8.400 (2.78), 8.421 (2.49),8.895 (10.41), 9.594 (1.37). 425 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (1.52), 0.008 (1.58), 1.509 (12.78), L1): 1.527(13.71), 1.536 (13.42), 1.554 Rt = 1.26 (12.80), 2.013 (0.92), 2.022(1.01), 2.032 min; MS (1.08), 2.039 (1.12), 2.049 (1.52), 2.056(ESIpos): (1.44), 2.085 (7.75), 2.172 (0.94), 2.184 m/z = 475 (1.30),2.196 (1.24), 2.206 d-19), 2.219 [M + H]⁺ (0.80), 2.240 (0.47), 2.327(0.45), 2.366 (0.47), 2.423 (16.00), 2.669 (0.46), 2.710 (0.40), 3.804(0.54), 3.823 (1.32), 3.840 (1.76), 3.859 (1.30), 3.876 (0.52), 4.201(0.51), 4.208 (0.72), 4.228 (2.09), 4236 (1.71), 4.249 (2.84), 4.259(2.77), 4.267 (1.88), 4.277 (1.91), 4.288 (0.56), 4.295 (0.68), 4.304(0.47), 5.246 (0.87), 5.260 (1.95), 5.280 (1.96), 5.294 (0.85), 5.754(7.58), 6.631 (2.13), 6.777 (3.89), 6.797 (4.26), 6.902 (1.75), 6.904(1.90), 6.923 (3.94), 6.939 (2.29), 6.942 (2.32), 7.143 (1.85), 7.147(2.06), 7.164 (3.17), 7.182 (1.50), 7.185 (1.53), 7.334 (3.33), 7.352(3.03), 7.618 (2.57), 7.641 (4.67), 7.664 (2.68), 8.442 (2.31), 8.457(2.47), 8.465 (2.46), 8.481 (2.28), 8.709 (12.28), 9.081 (3.16), 9.102(3.09). 426 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149(0.83), −0.008 (6.50), 0.008 L1): (7.02), 0.146 (0.83), 1.235 (0.67),1.508 Rt = 1.32 (14.93), 1.526 (15.98), 1.534 (16.00), min; MS 1.552(15.19), 2.051 (1.31), 2.073 (1.29), (ESIpos): 2.085 (2.88), 2.185(1.50), 2.198 (1.48), m/z = 515 2.207 (1.40), 2.220 (0.98), 2.327(0.90), [M + H]⁺ 2.366 (0.95), 2.669 (0.93), 2.710 (0.93), 3.828 (1.33),3.846 (1.74), 3.863 (1.31), 4.206 (0.79), 4.225 (2.29), 4.233 (1.88),4.252 (2.95), 4.259 (2.71), 4.267 (2.05), 4.276 (2.19), 4.295 (0.83),5.245 (0.93), 5.259 (2.12), 5.278 (2.17), 5.292 (0.98), 6.776 (4.48),6.796 (4.88), 6.905 (2.21), 6.924 (4.50), 6.940 (2.71), 7.144 (2.24),7.147 (2.40), 7.165 (3.71), 7.186 (1.83), 7.205 (3.79), 7.230 (3.98),7.333 (1.83), 7.346 (2.26), 7.362 (1.69), 7.687 (2.98), 7.710 (5.17),7.732 (3.05), 8.553 (2.71), 8.568 (2.88), 8.577 (2.88), 8.593 (2.71),8.764 (7.26), 9.111 (3.05), 9.132 (3.05). 428 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ 9.16 (L2): (d, J = 8.1 Hz, 1H), 8.72 (s, 1H), 8.69 Rt = 3.893(d, J = 1.9 Hz, 1H), 8.14 (d, J = 1.8 Hz, min; m/z = 1H), 7.71-7.66 (m,3H), 7.37 (d, J = 517/5519 7.9, 1.7 Hz, 1H), 7.17 (t, J = 8.5, 7.4, 1.7[M + H]+ Hz, 1H), 6.92 (t, J = 7.4, 1.2 Hz, 1H), 6.80 (d, J = 8.3, 1.2Hz, 1H), 5.23 (q, J = 5.8 Hz, 1H), 4.32-4.17 (m, 2H), 3.12 (s, 6H),2.26-2.14 (m, 1H), 2.10-1.99 (m, 1H). 430 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method 0.008 (1.38), 1.526 (14.80), 1.543 (16.00),L1): 1.552 (15.65), 1.570 (14.87), 2.029 Rt =1.23 (1.04), 2.038 (1.12),2.047 (1.19), 2.055 min; MS (1.21), 2.064 (1.68), 2.072 (1.42), 2.080(ESIpos): (1.02), 2.087 (0.71), 2.172 (0.65), 2.181 m/z = 459 (1.10),2.193 (1.48), 2.205 (1.42), 2.215 [M + H]⁺ (1.36), 2.228 (0.86), 3.828(0.64), 3.845 (1.58), 3.863 (2.07), 3.881 (1.54), 3.899 (0.60), 4.211(0.56), 4.219 (0.77), 4.239 (2.44), 4.247 (2.13), 4.258 (3.96), 4.267(4.09), 4.283 (2.26), 4.302 (0.73), 5.262 (1.01), 5.277 (2.33), 5.296(2.31), 5.311 (1.05), 6.781 (4.65), 6.801 (5.20), 6.912 (2.17), 6.930(4.68), 6.949 (2.74), 7.150 (2.33), 7.168 (3.75), 7.189 (1.74), 7.252(1.63), 7.258 (1.26), 7.276 (3.15), 7.282 (3.16), 7.301 (6.35), 7.318(6.19), 7.334 (1.02), 7.348 (4.05), 7.366 (3.67), 7.716 (2.63), 7.734(4.12), 7.755 (3.67), 7.834 (5.55), 7.851 (4.00), 8.438 (4.18), 8.459(3.86), 8.750 (14.88), 9.106 (3.97), 9.126 3.90). 431 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: (Method 0.008 (2.75), 1.530 (14.75), 1.548(16.00), L1): 1.556 (15.84), 1.574 (14.95), 2.034 Rt = 1.37 (1.00),2.043 (1.11), 2.053 (1.16), 2.059 min; MS (1.19), 2.069 (1.70), 2.077(1.41), 2.085 (ESIpos): (1.05), 2.191 (1.50), 2.203 (1.47), 2.213 m/z =525 (1.38), 2.226 (0.88), 2.328 (0.61), 2.366 [M + H]⁺ (0.66), 2.670(0.63), 2.710 (0.66), 3.843 (0.64), 3.860 (1.58), 3.878 (2.08), 3.896(1.53), 3.914 (0.61), 4.209 (0.61), 4.217 (0.75), 4.237 (2.49), 4.245(2.13), 4.257 (3.91), 4.266 (4.02), 4.282 (2.22), 4.301 (0.75), 5.258(1.02), 5.273 (2.30), 5.292 (2.31), 5.307 (1.03), 6.782 (4.49), 6.802(4.96), 6.913 (2.21), 6.931 (4.58), 6.950 (2.69), 7.151 (2.39), 7.168(3.68), 7.190 (1.78), 7.351 (3.93), 7.370 (3.58), 7.740 (2.83), 7.758(4.07), 7.761 (3.88), 7.779 (3.71), 7.891 (10.85), 7.902 (6.54), 7.909(5.57), 7.968 (6.30), 8.471 (4.19), 8.492 (3.75), 8.752 (15.12), 9.117(4.02), 9.138 (3.91). 432 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]:(Method 2.063 (0.44), 2.074 (1.74), 2.085 (0.57), L1): 2.091 (0.49),2.154 (16.00), 2.213 (0.54), Rt = 0.93 2.223 (0.51), 2.230 (0.52), 3.994(3.21), min; MS 4.221 (0.41), 4.226 (0.88), 4.232 (0.59), (ESIpos):4.243 (0.65), 4249 (0.52), 4.271 (0.53), m/z = 506 4.278 (0.67), 4.284(0.59), 4.291 (0.69), [M + H]⁺ 5.297 (0.75), 5.313 (0.74), 6.792 (1.44),6.793 (1.49), 6.808 (1.59), 6.810 (1.58), 6.918 (0.74), 6.920 (0.73),6.933 (1.47), 6.935 (1.43), 6.948 (0.86), 6.950 (0.81), 7.160 (0.72),7.163 (0.74), 7.177 (1.18), 7.191 (0.60), 7.194 (0.57), 7.404 (1.21),7.418 (1.15), 7.646 (0.87), 7.655 (9.82), 7.725 (1.04), 7.739 (1.43),7.741 (1.26), 7.756 (1.25), 7.863 (1.61), 7.866 (1.64), 7.877 (1.33),7.880 (1.26), 8.164 (1.66), 8.523 (1.33), 8.526 (1.33), 8.540 (1.27),8.543 (1.20), 8.920 (5.25), 9.432 (1.31), 9.448 (1.27). 438 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.41), −0.008 (3.62), 0.008L1): (3.26), 1.356 (1.83), 1.523 (14.77), 1.541 Rt = 1.37 (16.00), 1.550(15.57), 1.568 (14.88), min; MS 2.032 (1.00), 2.041 (1.04), 2.051(1.14), (ESIpos): 2.058 (1.00), 2.067 (1.68), 2.073 (2.66), m/z = 5092.084 (1.01), 2.170 (0.66), 2.183 (1.20), [M + H]⁺ 2.192 (1.42), 2.203(1.34), 2.213 (1.30), 2.225 (0.81), 2.323 (0.49), 2.327 (0.62), 2.366(0.55), 2.523 (1.52), 2.670 (0.68), 2.709 (0.55), 3.833 (0.60), 3.851(1.50), 3.869 (2.02), 3.887 (1.45), 3.905 (0.60), 4.211 (0.54), 4.219(0.74), 4.239 (2.40), 4.247 (2.04), 4.258 (3.83), 4.267 (3.95), 4.283(2.15), 4.301 (0.70), 5.260 (0.98), 5.274 (2.17), 5.294 (2.20), 5.308(0.96), 5.754 (6.17), 6.780 (4.02), 6.782 (4.25), 6.800 (4.58), 6.803(4.65), 6.912 (2.09), 6.915 (2.10), 6.931 (4.36), 6.933 (4.28), 6.949(2.67), 6.952 (2.58), 7.148 (2.17), 7.152 (2.29), 7.169 (3.48), 7.187(1.71), 7.190 (1.68), 7.351 (3.62), 7.370 (3.40), 7.717 (2.99), 7.735(4.36), 7.738 (3.68), 7.756 (4.00), 7.786 (15.35), 7.802 (15.29), 7.853(5.04), 7.855 (5.31), 7.870 (4.03), 7.873 (3.81), 7.907 (0.55), 7.9230.54), (8.444 (3.89), 8.464 (3.67), 8.762 (15.95), 9.108 (3.86), 9.129(3.76). 439 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(2.89), 0.008 (3.10), 1.826 (0.43), L1): 2.073 (1.46), 2.086 (0.91),2.327 (0.43), Rt = 1.10 2.366 (0.59), 2.670 (0.47), 2.710 (0.59), min;MS 4.178 (0.90), 5.127 (1.22), 5.141 (1.19), (ESIpos): 6.747 (2.96),6.767 (3.31), 6.836 (0.98), m/z = 560 6.920 (0.57), 7.045 (0.47), 7.124(1.50), [M + H]⁺ 7.145 (2.50), 7.162 (1.27), 7.258 (0.57), 7.333 (0.67),7.467 (0.72), 7.672 (7.22), 7.676 (16.00), 7.682 (6.08), 7.685 (3.72),7.732 (2.26), 7.750 (2.96), 7.753 (3.13), 7.771 (3.12), 7.911 (3.10),7.929 (5.80), 7.932 (5.43), 7.946 (3.43), 8.870 (1.48), 8.885 (1.41),9.005 (5.27), 12.563 (0.65). 444 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (3.30), 0.008 (2.88), 1.528 (9.79), L1): 1.546(10.48), 1.555 (10.17), 1.573 Rt = 1.30 (9.77), 2.017 (0.68), 2.025(0.71), 2.035 min; MS (0.76), 2.043 (0.78), 2.052 (1.09), 2.060(ESIpos): (0.90), 2.068 (0.66), 2.162 (0.45), 2.171 m/z = 489 (0.73),2.184 (1.01), 2.196 (0.94), 2.205 [M + H]⁺ (0.87), 2.219 (0.57), 2.327(0.73), 2.346 (16.00), 2.366 (0.80), 2.523 (1.25), 2.665 (0.40), 2.669(0.54), 2.710 (0.61), 3.841 (0.97), 3.859 (1.27), 3.877 (0.94), 4.211(0.50), 4.231 (1.58), 4.239 (1.35), 4250 (2.53), 4.259 (2.64), 4.275(1.46), 4.294 (0.47), 5.249 (0.64), 5.264 (1.44), 5.283 (1.46), 5.297(0.61), 6.775 (2.69), 6.793 (2.86), 6.795 (2.95), 6.901 (1.37), 6.904(1.39), 6.920 (2.83), 6.922 (2.83), 6.938 (1.75), 6.941 (1.70), 7.141(1.39), 7.145 (1.49), 7.162 (2.34), 7.180 (2.86), 7.183 (2.93), 7.195(1.84), 7.199 (1.79), 7.340 (2.41), 7.357 (2.27), 7.451 (1.63), 7.455(1.58), 7.468 (1.65), 7.472 (1.56), 7.716 (1.16), 7.734 (3.42), 7.753(6.32), 7.756 (5.45), 7.768 (1.30), 8.457 (2.15), 8.462 (2.08), 8.476(2.08), 8.482 (1.96), 8.687 (9.91), 9.113 (2.57), 9.133 (2.50). 446LC-MS ¹H-NMR (500 MHz DMSO-d6) δ [ppm]: (Method 0.006 (0.83), 1.528(15.59), 1.542 (16.00), L1): 1.554 (15.53), 1.569 (15.22), 2.022 Rt =1.28 (0.59), 2.029 (0.75), 2.035 (1.20), 2.042 min; MS (1.26), 2.049(1.35), 2.055 (1.35), 2.063 (ESIpos): (1.74), 2.069 (1.50), 2.076(1.05), 2.082 m/z = 475 (0.74), 2.178 (0.75), 2.185 (1.16), 2.195 [M +H]⁺ (1.62), 2.205 (1.56), 2.212 (1.50), 2.222 (1.07), 2.229 (0.80),2.239 (0.53), 3.836 (0.65), 3.851 (1.49), 3.865 (1.95), 3.879 (1.44),3.893 (0.59), 4.218 (0.74), 4.224 (0.93), 4.240 (2.73), 4.246 (2.13),4256 (2.85), 4.261 (3.43), 4.268 (2.78), 4.274 (2.18), 4.281 (2.36),4.290 (0.72), 4.296 (0.86), 4.303 (0.60), 5.266 (1.16), 5.278 (2.45),5.293 (2.39), 5.305 (1.07), 5.753 (2.04), 6.783 (4.78), 6.799 (5.11),6.916 (2.31), 6.931 (4.75), 6.945 (2.64), 7.151 (2.25), 7.154 (2.34),7.168 (3.85), 7.182 (1.85), 7.184 (1.80), 7.350 (4.06), 7.364 (3.73),7.492 (2.91), 7.509 (5.77), 7.528 (4.33), 7.571 (2.42), 7.575 (2.60),7.581 (2.67), 7.585 (2.75), 7.593 (1.86), 7.598 (1.61), 7.602 (1.61),7.712 (2.90), 7.726 (4.39), 7.743 (3.94), 7.772 (3.91), 7.776 (3.80),7.786 (3.97), 7.790 (3.76), 7.806 (5.60), 7.819 (3.92), 8.418 (4.24),8.434 (3.91), 8.736 (14.80, 9.100 (4.07), 9.116 (3.94). 447 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 0.008 (1.67), 0.008 (1.74), 1.531(11.51), L1): 1.549 (12.60), 1.558 (16.00), 1.576 Rt = 1.27 (15.03),1.860 (10.28), 1.875 (10.05), min; MS [2.011 (1.17), 2.019 (1.28), 2.028(1.43), (ESIpos): 2.035 (1.35), 2.045 (1.78), 2.053 (1.52), m/z = 4512.061 (1.12), 2.069 (0.78), 2.085 (3.05), [M + H]⁺ 2.168 (3.67), 2.179(1.64), 2.191 (1.75), 2.201 (1.41), 2.214 (1.00), 2.234 (0.57), 2.285(42.65), 2.292 (14.54), 2.327 (0.48), 2.669 (0.41), 3.818 (0.64), 3.835(1.53), 3.853 (2.04), 3.871 (1.49), 3.888 (0.61), 4.199 (0.69), 4.207(0.86), 4.227 (2.74), 4.235 (2.35), 4.247 (4.38), 4.256 (4.48), 4.272(2.50), 4.284 (0.69), 4.290 (0.91), 4.299 (0.59), 5.246 (1.09), 5.260(2.43), 5.280 (2.46), 5.294 (1.09), 5.754 (9.81), 6.772 (4.79), 6.792(5.26), 6.894 (1.96), 6.912 (4.26), 6.932 (4.96), 6.950 (2.92), 7.005(0.53), 7.090 (2.60), 7.109 (4.90), 7.141 (3.48), 7.155 (5.80), 7.175(3.08), 7.303 (0.65), 7.324 (3.77), 7.343 (2.96), 7.412 (0.62), 7.431(0.77), 7.562 (4.28), 7.565 (4.58), 7.580 (5.85), 7.582 (5.76), 7.673(4.25), 7.691 (3.82), 7.694 (4.77), 7.712 (3.30), 8.378 (4.53), 8.397(4.13), 8.616 (12.23), 9.077 (4.12), 9.098 (4.04). 448 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: ] (Method −0.008 (2.15), 0.008 (2.01), 1.526(8.21), L1): 1.543 (8.87), 1.552 (8.65), 1.570 (8.25), Rt = 1.27 2.028(0.57), 2.037 (0.60), 2.047 (0.61), min; MS 2.053 (0.63), 2.063 (0.89),2.071 (0.76), (ESIpos): 2.079 (0.53), 2.179 (0.59), 2.192 (0.77), m/z =455 2.203 (0.76), 2.213 (0.69), 2.227 (0.52), [M + H]⁺ 2.366 (0.49),2.388 (16.00), 3.842 (0.82), 3.860 (1.10), 3.878 (0.79), 4.239 (1.31),4.248 (1.14), 4 258 (2.05), 4.267 (2.19), 4.282 (1.16), 5.261 (0.56),5.276 (1.18), 5.295 (1.18), 5.310 (0.53), 6.778 (220), 6.781 (2.35),6.799 (2.50), 6.801 (2.55), 6.909 (1.16), 6.912 (1.18), 6.928 (2.39),6.930 (2.36), 6.946 (1.47), 6.949 (1.40), 7.052 (1.36), 7.076 (1.37),7.146 (1.22), 7.150 (1.28), 7.167 (3.29), 7.190 (2.18), 7.204 (3.78),7.346 (1.99), 7.365 (1.85), 7.691 (1.43), 7.709 (2.47), 7.731 (2.48),7.763 (2.94), 7.766 (3.19), 7.781 (1.79), 7.784 (1.62), 8.393 (2.00),8.396 (2.06), 8.415 (1.96), 8.418 (1.84), 8.721 (8.75), 9.097 (2.09),9.117 (2.02). 449 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (0.44), −0.008 (3.46), 0.008 L1): (3.37), 0.146 (0.41), 1.522(14.76), 1.540 Rt = 1.27 (16.00), 1.548 (15.61), 1.566 (14.88), min; MS2.014 (0.46), 2.030 (1.02), 2.038 (1.07), (ESIpos): 2.048 (1.14), 2.055(1.14), 2.064 (1.61), m/z = 477 2.072 (1.35), 2.080 (0.98), 2.088(0.68), [M + H]⁺ 2.171 (0.62), 2.181 (1.07), 2.193 (1.41), 2.205 (1.37),2.214 (1.27), 2.229 (0.85), 2.235 (0.72), 2.248 (0.46), 2.327 (0.52),2.366 (0.54), 2.669 (0.59), 2.710 (0.55), 3.826 (0.62), 3.843 (1.51),3.861 (2.02), 3.879 (1.48), 3.896 (0.57), 4.210 (0.55), 4.218 (0.76),4.238 (2.44), 4.246 (2.05), 4.258 (3.89), 4.267 (3.93), 4.283 (2.16),4.295 (0.59), 4.302 (0.73), 5.261 (0.98), 5.276 (2.18), 5.296 (2.20),5.310 (0.99), 6.782 (4.05), 6.802 (4.47), 6.911 (2.03), 6.914 (2.08),6.930 (4.31), 6.932 (4.24), 6.948 (2.63), 6.951 (2.50), 7.148 (2.11),7.152 (2.23), 7.169 (3.50), 7.187 (1.71), 7.190 (1.69), 7.348 (3.67),7.366 (3.41), 7.538 (4.10), 7.546 (1.25), 7.555 (4.44), 7.561 (4.49),7.578 (4.34), 7.587 (0.80), 7.594 (0.47), 7.716 (2.81), 7.734 (4.18),7.737 (3.56), 7.756 (3.90), 7.834 (4.93), 7.836 (5.20), 7.851 (3.82),8.441 (3.93), 8.460 (3.67), 8.754 (14.49), 9.107 (3.76), 9.128 (3.64).450 LC-MS ¹H-NMR (400 MHz DMSO-d6) δ [ppm]: (Method −0.008 (3.44), 0.008(2.25), 1.528 (14.93), L1): 1.22 1.546 (16.00), 1.555 (15.22), 1.573 Rt= (14.27), 2.003 (0.56), 2.018 (1.14), 2.027 min; MS (1.17), 2.036(1.20), 2.044 (1.21), 2.053 (ESIpos): (1.64), 2.061 (1.36), 2.069(0.97), 2.077 m/z = 477 (0.66), 2.165 (0.73), 2.174 (1.14), 2.187 [M +H]⁺ (1.49), 2.198 (1.42), 2.208 (1.32), 2.219 (0.87), 2.229 (0.70),2.241 (0.45), 2.524 (1.57), 3.824 (0.68), 3.841 (1.51), 3.859 (1.93),3.877 (1.40), 3.895 (0.55), 4.203 (0.69), 4.210 (0.92), 4.230 (2.57),4.238 (2.17), 4.250 (3.83), 4.260 (3.63), 4.267 (2.17), 4.276 (2.10),4.288 (0.60), 4.295 (0.73), 4.304 (0.47), 5.251 (1.07), 5.266 (2.23),5.285 (2.13), 5.300 (0.94), 6.774 (3.85), 6.776 (3.91), 6.794 (4.27),6.796 (4.17), 6.902 (2.14), 6.905 (2.10), 6.921 (4.27), 6.923 (4.08),6.939 (2.56), 6.942 (2.34), 7.142 (2.24), 7.146 (2.30), 7.163 (3.45),7.181 (1.81), 7.185 (1.77), 7.207 (1.78), 7.215 (1.67), 7.229 (1.65),7.241 (0.79), 7.340 (3.62), 7.359 (3.30), 7.567 (0.70), 7.575 (0.84),7.582 (0.97), 7.590 (1.44), 7.595 (1.32), 7.603 (1.42), 7.610 (1.33),7.616 (1.34), 7.623 (0.84), 7.631 (0.75), 7.639 (0.66), 7.743 (2.63),7.761 (4.44), 7.782 (4.33), 7.815 (5.04), 7.818 (5.19), 7.832 (3.04),8.495 ( 3.72), 8.498 (3.67), 8.516 (3.54), 8.519 (3.18), 8.716 9.146(3.50). 451 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008(2.87), 0.008 (2.99), 1.535 (13.93), L1): 1.553 (15.28), 1.562 (16.00),1.580 Rt = 1.32 (15.01), 2.015 (11.45), 2.043 (1.86), min; MS 2.073(0.70), 2.086 (1.48), 2.156 (0.80), (ESIpos): 2.165 (1.28), 2.178(1.76), 2.190 (1.65), m/z = 505 2.199 (1.57), 2.211 (1.06), 2.220(0.84), [M + H]⁺ 2.233 (0.55), 2.301 (1.08), 2.327 (0.40), 3.833 (0.67),3.851 (1.64), 3.868 (2.17), 3.886 (1.60), 3.904 (0.65), 4.194 (0.64),4.202 (0.82), 4.222 (2.46), 4.230 (2.05), 4.244 (3.50), 4.254 (3.47),4.261 (2.45), 4.271 (2.47), 4.282 (0.76), 4.289 (0.90), 4.298 (0.61),5.241 (1.14), 5.256 (2.55), 5.275 (2.57), 5.290 (1.14), 5.754 (11.28),6.769 (4.42), 6.771 (4.75), 6.789 (5.07), 6.792 (5.21), 6.890 (2.32),6.892 (2.35), 6.909 (4.87), 6.911 14.82), 6.927 (2.95), 6.930 (2.82),7.136 (2.44), 7.140 (2.63), 7.157 (4.04), 7.175 (2.01), 7.178 (1.96),7.323 (4.16), 7.341 (3.86), 7.398 (0.50), 7.402 (0.46), 7.439 (2.71),7.483 (0.53), 7.535 (2.86), 7.555 (3.81), 7.665 (5.56), 7.668 (4.53),7.683 (8.94), 7.719 (5.14), 7.737 (3.59), 7.741 (5.33), 7.758 (3.09),8.445 (4.24), 8.448 (4.48), 8.467 (4.12), 8.469 (3.99), 8.640 (15.04),9.087 (2.78), 9.107 (2.71). 453 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (2.92), 0.008 (2.81), 1.528 (13.71), L1): 1.546 (14.79),1.555 (16.00), 1.573 Rt = 1.29 (15.23), 1.995 (0.48), 2.011 (1.10),2.019 min; MS (1.19), 2.029 (1.25), 2.037 (1.25), 2.046 (ESIpos):(1.76), 2.054 (1.47), 2.062 (1.08), 2.158 m/z = 491 (0.66), 2.167(1.14), 2.179 (1.56), 2.191 [M + H]⁺ (1.52), 2.201 (1.38), 2.215 (0.95),2.224 (0.79), 2.234 (0.51), 2.327 (0.53), 2.366 (0.64), 2.522 (1.30),2.669 (0.57), 2.710 (0.64), 3.818 (0.59), 3.836 (1.47), 3.854 (1.91),3.871 (1.43), 3.889 (0.57), 4.199 (0.57), 4.207 (0.81), 4.227 (2.55),4.235 (2.24), 4.246 (4.18), 4.255 (4.37), 4.271 (2.40), 4.283 (0.66),4.290 (0.79), 4.299 (0.51), 5.245 (1.03), 5.259 (2.33), 5.279 (2.42),5.294 (1.12), 6.771 (4.44), 6.792 (4.88), 6.895 (2.11), 6.897 (2.18),6.913 (4.53), 6.916 (4.55), 6.932 (2.84), 6.934 (2.70), 7.137 (2.24),7.141 (2.42), 7.158 (3.78), 7.176 (1.82), 7.179 (1.82), 7.331 (3.49),7.349 (3.32), 7.446 (2.55), 7.457 (3.58), 7.470 (1.80), 7.478 (1.08),7.484 (1.54), 7.489 (1.34), 7.495 (1.12), 7.505 (4.07), 7.511 (3.08),7.526 (6.37), 7.533 (5.60), 7.585 (4.48), 7.599 (1.47), 7.607 (2.68),7.622 (0.88), 7.693 (1.47), 7.698 (2.37), 7.711 (6.81), 7.716 (6.90),7.719 (7.23), 7.739 (5.49), 7.757 (2.24), 8.456 (3.58), 8.460 (3.76),8.476 (3.45), 8.480 (3.43), 8.661 (11.47), 8.729 (0.46), 9.113 (4.07),9.134 (4.00). 454 LC-MS ¹H-NMR (500 MHz, DMSO-d6): δ (Method [ppm] =13.33 (br s, 1H), 8.92 (s, 1H), L1): 8.75 (d, 1H), 8.12-7.96 (m, 2H),7.90 Rt = 1.13 (dd, 1H), 7.73-7.66 (m, 5H), 7.12 (t, min; MS 1H), 6.92(d, 1H), 6.83 (t, 1H), 6.73 (dd, (ESIpos): 1H), 5.12-5.06 (m, 1H),4.18-4.07 (m, m/z = 515 1H), 3.99 (ddd, 1H), 2.56-2.52 (m, 1H), [M + H]⁺2.09-1.96 (m, 1H), 1.78 (td, 1H) 455 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ[ppm]: (Method −0.008 (3.81), 0.008 (2.57), 0.853 (0.46), L1): 1.235(2.17), 1.300 (0.52), 1.316 (0.51), Rt = 1.36 1.398 (1.60), 1.513(14.80), 1.531 (16.00), min; MS 1.540 (15.55), 1.558 (14.28), 2.016(ESIpos): (1.21), 2.023 (1.32), 2.033 (1.33), 2.040 m/z = 509 (1.33),2.050 (1.72), 2.057 (1.47), 2.181 [M + H]⁺ (1.67), 2.194 (1.60), 2.203(1.49), 2.216 (1.01), 2.327 (0.52), 2.669 (0.63), 2.710 (0.49), 3.829(0.77), 3.847 (1.66), 3.865 (2.13), 3.882 (1.55), 3.900 (0.64), 4.205(1.06), 4.225 (2.72), 4.233 (2.29), 4.246 (3.46), 4.265 (2.32), 4.274(2.31), 4.293 (0.84), 5.242 (1.17), 5.256 (2.44), 5.276 (2.34), 5.290(1.06), 5.754 (5.78), 6.776 (4.38), 6.795 (4.71), 6.900 (2.25), 6.919(4.51), 6.937 (2.66), 7.146 (2.46), 7.164 (3.72), 7.181 (1.83), 7.335(3.97), 7.353 (3.56), 7.505 (11.79), 7.509 (11.98), 7.682 (3.19), 7.692(4.34), 7.697 (7.04), 7.702 (5.43), 7.705 (5.86), 7.728 (2.85), 8.525(2.64), 8.540 (2.80), 8.549 (2.69), 8.564 (2.43), 8.745 (13.37), 9.099(3.97), 9.120 (3.77). 477 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 0.837 (0.43), 0.854 (0.54), 0.891 (0.49), L1): 1.141 (0.54),1.235 (1.16), 1.317 (0.60), Rt = 1.26 1.343 (0.89), 1.359 (1.03), 1.519(11.49), min; MS 1.522 (11.46), 1.536 (12.92), 1.541 (ESIpos): (13.45),1.548 (16.00), 1.566 (14.61), m/z = 509 2.000 (1.38), 2.008 (1.47),2.024 (1.68), [M + H]⁺ 2.035 (2.05), 2.174 (1.95), 2.186 (1.92), 2.196(1.86), 2.210 (1.48), 2.328 (0.62), 2.366 (0.58), 2.669 (0.65), 2.710(0.54), 3.849 (1.72), 3.858 (1.72), 4.196 (1.05), 4.216 (3.08), 4.224(2.77), 4.240 (4.11), 4.265 (2.93), 4.284 (1.16), 5.232 (1.14), 5.247(2.57), 5.264 (2.59), 6.767 (4.85), 6.787 (5.50), 6.888 (2.50), 6.906(5.25), 6.924 (3.19), 7.137 (2.79), 7.155 (4.52), 7.172 (2.28), 7.316(2.70), 7.326 (2.95), 7.333 (2.84), 7.343 (2.62), 7.358 (2.21), 7.361(2.23), 7.380 (4.65), 7.399 (3.04), 7.403 (2.97), 7.457 (2.43), 7.469(2.86), 7.477 (4.20), 7.489 (4.31), 7.496 (2.32), 7.508 (2.35), 7.694(3.04), 7.717 (5.27), 7.739 (7.60), 7.758 (4.31), 7.762 (4.11), 8.555(2.91), 8.570 (3.22), 8.579 (3.15), 8.594 (2.82), 8.675 (6.93), 8.686(7.13), 9.115 (4.16), 9.135 (3.98). 478 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method −0.008 (1.30), 0.008 (1.39), 1.157 (0.78), L1): 1.175(1.56), 1.192 (0.80), 1.398 (0.65), Rt = 1.31 1.988 (3.13), 2.002(0.44), 2.012 (0.46), min; MS 2.019 (0.47), 2.029 (0.65), 2.036 (0.56),(ESIpos): 2.044 (0.40), 2.086 (1.10), 2.135 (0.42), m/z = 475 2.148(0.61), 2.160 (0.56), 2.169 (0.53), [M + H]⁺ 4.021 (0.69), 4.038 (0.69),4.216 (0.98), 4.223 (0.77), 4.236 (1.07), 4.243 (1.18), 4.250 (1.04),4.257 (0.80), 4.266 (0.84), 5.227 (0.88), 5.247 (0.89), 5.677 (1.55),5.681 (1.65), 5.722 (1.60), 5.725 (1.76), 5.754 (2.74), 5.810 (1.65),5.813 (1.59), 5.839 (1.68), 5.842 (1.68), 6.775 (1.68), 6.796 (1.85),6.899 (0.83), 6.917 (1.72), 6.934 (1.01), 7.142 (0.82), 7.146 (0.88),7.163 (1.40), 7.180 (0.67), 7.184 (0.68), 7.305 (1.47), 7.324 (1.41),7.331 (1.46), 7.360 (1.32), 7.376 (1.31), 7.405 (1.17), 7.664 (16.00),7.741 (1.18), 7.759 (1.71), 7.780 (1.56), 7.895 (1.87), 7.898 (2.02),7.913 (1.52), 7.916 (1.50), 8.242 (1.70), 8.245 (1.76), 8.262 (1.59),8.266 (1.54), 8.909 (5.42), 9.001 (1.53), 9.021 (1.48). 479 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 1.519 (14.64), 1.536 (16.00), 1.545L1): (15.88), 1.563 (14.91), 2.013 (1.08), 2.021 Rt = 1.29 (1.17), 2.031(1.28), 2.038 (1.29), 2.048 min; MS (1.72), 2.055 (1.49), 2.063 (1.07),2.071 (ESIpos): (0.76), 2.161 (0.68), 2.170 (1.10), 2.182 m/z = 525(1.58), 2.194 (1.51), 2.203 (1.44), 2.216 [M + H]⁺ (1.01), 2.237 (0.51),3.827 (0.66), 3.845 (1.63), 3.863 (2.19), 3.881 (1.61), 3.898 (0.66),4.196 (0.63), 4.203 (0.84), 4.223 (2.53), 4.230 (2.07), 4.249 (3.21),4.256 (2.97), 4.264 (2.19), 4.273 (2.28), 4.284 (0.71), 4.292 (0.84),4.300 (0.57), 5.244 (1.06), 5.258 (2.41), 5.277 (2.44), 5.292 (1.07),6.774 (4.57), 6.795 (5.08), 6.898 (2.22), 6.916 (4.75), 6.935 (2.76),7.143 (2.39), 7.162 (3.87), 7.182 (1.81), 7.329 (4.15), 7.348 (3.78),7.421 (5.41), 7.454 (3.25), 7.466 (3.77), 7.486 (4.52), 7.607 (4.06),7.627 (6.11), 7.646 (2.60), 7.677 (2.67), 7.700 (5.22), 7.723 (2.75),8.510 (2.55), 8.525 (2.75), 8.534 (2.70), 8.549 (2.46), 8.707 (13.60),9.091 (4.09), 9.111 (3.99). 487 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.150 (0.50), 0.146 (0.45), 0.852 (0.69), L12): 1.234 (3.42),1.299 (0.54), 1.518 (13.51), Rt = 1.56 1.536 (14.79), 1.544 (16.00),1.562 min; MS (14.83), 2.006 (1.08), 2.014 (1.24), 2.023 (ESIpos):(1.45), 2.031 (1.35), 2.040 (1.61), 2.049 m/z = 495 (1.65), 2.056(1.35), 2.182 (1.69), 2.194 [M + H]⁺ (1.63), 2.203 (1.56), 2.217 (1.13),2.327 (0.52), 2.669 (0.48), 3.839 (1.13), 3.857 (1.54), 3.866 (1.54),3.884 (1.08), 4.197 (0.78), 4.223 (2.32), 4.246 (3.38), 4.255 (2.97),4.263 (2.34), 4.272 (2.41), 4.291 (0.93), 5.256 (2.25), 5.270 (2.26),6.773 (4.60), 6.793 (5.14), 6.897 (2.13), 6.916 (4.58), 6.934 (2.71),7.144 (2.47), 7.162 (4.06), 7.180 (1.89), 7.279 (1.78), 7.323 (2.19),7.342 (4.10), 7.360 (2.08), 7.638 (0.65), 7.646 (0.80), 7.661 (1.58),7.674 (1.60), 7.687 (1.61), 7.702 (0.89), 7.710 (0.84), 7.724 (2.62),7.747 (4.86), 7.770 (2.69), 8.596 (2.77), 8.611 (2.95), 8.620 (2.95),8.635 (2.69), 8.736 (6.87), 8.747 (7.18), 9.121 (4.19), 9.142 (4.12).488 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.149 (0.83),−0.008 (6.41), 0.008 L12): (6.73), 0.146 (0.80), 1.141 (0.40), 1.157 Rt= 1.60 (0.99), 1.175 (1.92), 1.193 (0.96), 1.235 min; MS (0.88), 1.398(2.11), 1.522 (14.80), 1.540 (ESIpos): (16.00), 1.548 (15.71), 1.566(14.90), m/z = 509 1.988 (3.66), 2.013 (1.04), 2.022 (1.15), [M + H]⁺2.031 (1.20), 2.048 (1.63), 2.056 (1.39), 2.180 (1.52), 2.192 (1.44),2.202 (1.39), 2.215 (0.91), 2.327 (0.75), 2.670 (0.83), 3.836 (0.59),3.853 (1.50), 3.871 (2.03), 3.889 (1.44), 3.907 (0.59), 4.021 (0.83),4.038 (0.83), 4.202 (0.85), 4.222 (2.51), 4.230 (1.98), 4.248 (2.86),4.255 (2.80), 4.263 (2.06), 4.272 (2.16), 4.291 (0.88), 5.240 (0.99),5.255 (2.16), 5.275 (2.22), 5.290 (1.04), 6.774 (4.51), 6.795 (4.99),6.895 (2.11), 6.897 12.19), 6.916 (4.43), 6.932 (2.70), 6.935 (2.62),7.140 (2.22), 7.143 (2.32), 7.161 (3.58), 7.178 (1.82), 7.182 (1.84),7.330 (3.69), 7.348 (3.42), 7.691 (2.96), 7.714 (6.17), 7.737 (5.96),7.752 (11.25), 7.767 (7.93), 7.802 (3.53), 7.817 (2.03), 8.524 (2.59),8.538 (2.78), 8.547 (2.83), 8.563 (2.59), 8.710 (15.17), 9.096 (3.79),9.117 (3.69). 489 LC-MS ¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: (Method 1.670(0.68), 1.681 (1.19), 1.688 (1.28), L1): 1.692 (1.29), 1.700 (1.35),1.704 (1.28), Rt = 1.38 1.710 (0.81), 1.938 (0.60), 1.946 (0.88), min;MS 1.952 (1.34), 1.960 (1.43), 1.966 (1.42), (ESIpos): 1.975 (1.17),1.980 (0.77), 1.983 (0.76), m/z = 531 1.988 (0.57), 3.957 (1.00), 3.961(1.18), [M + H]⁺ 3.975 (2.40), 3.989 (1.44), 3.993 (1.28), 4.105 (1.24),4.110 (1.53), 4.116 (1.46), 4.122 (2.04), 4.128 (1.21), 4.135 (1.18),4.139 (1.00), 5.034 (0.99), 5.044 (2.14), 5.057 (2.17), 5.067 (0.99),5.747 (5.67), 6.713 (4.06), 6.726 (4.34), 6.811 (1.78), 6.823 (4.08),6.835 (2.55), 6.899 (3.76), 6.912 (2.80), 7.101 (1.95), 7.113 (3.41),7.126 (1.67), 7.259 (4.11), 7.267 (4.21), 7.669 (9.16), 7.672 (9.94),7.681 (16.00), 7.684 (12.40), 7.691 (2.86), 7.705 (4.02), 7.717 (3.37),7.795 (5.01), 7.798 (4.25), 7.803 (4.06), 7.806 (6.59), 7.892 (4.03),7.894 (4.31), 7.904 (3.65), 7.906 (3.78), 8.700 (3.70), 8.714 (3.63),8.975 (11.32). 493 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm] (Method−0.008 (1.23), 0.008 (1.23), 1.235 (0.64), L1): 2.073 (0.59), 3.063(16.00), 3.283 (0.84), Rt = 1.07 3.332 (1.24), 3.707 (0.83), 3.726(0.96), min; MS 3.735 (0.87), 3.754 (0.75), 5.790 (0.75), (ESIpos):5.810 (0.75), 7.121 (0.41), 7.124 (0.46), m/z = 494 7.140 (0.96), 7.143(1.04), 7.158 (0.66), [M + H]⁺ 7.161 (0.71), 7.229 (0.45), 7.248 (1.01),7.266 (0.67), 7.288 (1.37), 7.306 (0.61), 7.389 (1.07), 7.408 (0.94),7.640 (7.94), 7.651 (2.13), 7.655 (2.38), 7.673 (1.13), 7.798 (1.17),7.801 (1.35), 7.816 (1.24), 7.819 (1.23), 8.233 (0.99), 8.236 (1.09),8.254 (0.96), 8.258 (0.98), 8.581 (0.48), 8.683 (3.65), 9.242 (0.98),9.263 (0.98). 494 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (2.50), 1.234 (1.19), 1.797 (2.72), L1): 1.813 (2.16), 1.831(1.22), 2.017 (3.78), Rt = 1.44 2.027 (5.23), 2.042 (4.61), 2.052(4.11), min; MS 2.118 (2.71), 2.141 (2.97), 2.166 (2.48), (ESIpos):2.174 (2.13), 2.187 (2.12), 2.198 (1.81), m/z = 517 2.209 (1.47), 2.242(0.49), 3.802 (1.35), [M + H]⁺ 3.825 (1.96), 3.849 (1.31), 4.211 (0.45),4.219 (0.64), 4.238 (2.26), 4.247 (2.23), 4.257 (3.32), 4.265 (3.75),4.279 (2.16), 4.297 (0.65), 4.306 (0.41), 5.268 (0.94), 5.283 (2.12),5.303 (2.15), 5.317 (0.95), 5.754 (0.50), 6.780 (3.97), 6.800 (4.42),6.906 (1.93), 6.924 (4.12), 6.943 (2.41), 7.146 (1.92), 7.150 (2.10),7.167 (3.36), 7.185 (1.57), 7.188 (1.61), 7.334 (3.58), 7.352 (3.29),7.615 (11.95),7.620 (16.00), 7.643 (3.83), 7.648 (5.15), 7.652 (2.49),7.709 (2.30), 7.728 (3.62), 7.749 (3.21), 7.835 (4.99), 7.853 (3.64),8.277 (3.63), 8.297 (3.29), 8.751 (13.22), 9.097 (3.72), 9.117 (3.65).519 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm] (Method 1.157 (2.50), 1.175(5.02), 1.193 (2.67), L1): 1.234 (1.23), 1.540 (3.03), 1.988 (9.10), Rt= 0.91 2.063 (2.50), 2.079 (2.80), 2.198 (2.93), min; MS 2.221 (2.26),2.328 (0.95), 2.366 (0.77), (ESIpos): 2.670 (0.84), 2.694 (0.44), 2.710(0.45), m/z = 518 2.961 (1.24), 2.983 (1.72), 3.003 (1.27), [M + H]⁺3.192 (2.79), 3.209 (2.69), 3.510 (0.78), 3.568 (1.00), 3.687 (1.02),3.944 (1.29), 3.964 1.72), 3.984 (1.23), 4.003 (1.27), 4.020 (2.57),4.038 (2.55), 4.056 (1.22), 4.264 (6.12), 5.271 (1.44), 5.287 (3.19),5.305 (3.16), 5.320 (1.42), 6.779 (5.67), 6.799 (6.10), 6.907 (2.67),6.926 (5.43), 6.944 (3.19), 7.147 (3.24), 7.166 (5.08), 7.185 (2.43),7.345 (4.52), 7.364 (4.26), 7.621 (16.00), 7.641 (6.46), 7.646 (7.29),7.666 (3.01), 7.691 (2.20), 7.711 (3.99), 7.731 (3.09), 7.832 (6.29),7.849 (4.99), 7.890 (0.71), 7.908 (0.56), 8.417 (0.70), 8.654 (2.62),8.675 (2.44), 8.759 (14.38), 8.912 (1.06), 9.129 (2.46), 9.139 (2.89),9.149 (2.97), 9.159 (2.67). 520 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.735 (0.54), 1.741 (0.60), 1.753 (0.64), L1): 1.769 (0.75),1.775 (0.68), 1.785 (0.45), Rt = 1.26 1.982 (0.46), 1.994 (0.70), 2.008(0.73), min; MS 2.016 (0.72), 2.029 (0.56), 3.944 (0.51), (ESIpos):3.950 (0.61), 3.972 (1.56), 3.993 (0.80), m/z = 565 3.999 (0.65), 4.118(0.63), 4.125 (0.83), [M + H]⁺ 4.134 (0.77), 4.142 (0.98), 4.153 (0.60),4.162 (0.60), 4.169 (0.47), 5.070 (0.51), 5.084 (1.14), 5.104 (1.15),5.118 (0.50), 5.754 (1.74), 6.728 (2.15), 6.748 (2.40), 6.803 (0.98),6.822 (2.24), 6.840 (1.42), 6.951 (2.12), 6.969 (1.59), 7.106 (1.04),7.127 (1.79), 7.145 (0.87), 7.684 (16.00), 7.737 (1.24), 7.757 (2.35),7.776 (1.77), 7.862 (1.30), 7.929 (2.60), 7.940 (3.02), 7.943 (2.91),7.961 (2.06), 8.010 (7.93), 8.156 (1.16), 8.519 (6.04), 8.866 (2.07),8.886 (2.02), 8.999 (6.20). 539 LC-MS ¹H-NMR (400 MHz DMSO-d6) δ [ppm]:(Method 0.008 (2.51), 1.235 (0.43), 1.676 (1.54), L1): 1.713 (2.60),1.751 (1.67), 2.057 (0.97), Rt = 1.28 2.072 (1.11), 2.085 (1.87), 2.218(1.33), min; MS 2.231 (1.31), 2.240 (1.26), 2.252 (0.92), (ESIpos):2.327 (0.56), 2.366 (0.60), 2.429 (2.14), m/z = 533 2.460 (2.25), 2.670(0.69), 2.710 (0.67), [M + H]⁺ 3.464 (1.07), 3.493 (1.97), 3.520 (2.14),3.546 (2.15), 3.575 (1.18), 3.738 (1.26), 4.010 (3.17), 4.023 (2.81),4.038 (2.85), 4.219 (0.82), 4.240 (2.21), 4.247 (1.78), 4.260 (2.15),4.268 (2.70), 4.279 (2.21), 4.295 (1.97), 5.293 (0.94), 5.307 (2.08),5.327 (2.08), 5.342 (0.90), 5.754 (5.00), 6.785 (3.97), 6.804 (4.38),6.918 (1.97), 6.937 (4.07), 6.956 (2.40), 7.158 (2.10), 7.176 (3.37),7.193 (1.61), 7.405 (3.52), 7.423 (3.20), 7.613 (13.15), 7.617 (16.00),7.648 (4.20), 7.653 (5.68), 7.748 (2.29), 7.766 (3.65), 7.787 (3.20),7.856 (4.95), 7.874 (3.52), 8.510 (3.43), 8.531 (3.17), 8.777 (12.63),9.140 (3.54), 9.161 (3.54). 552 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm](Method 0.006 (2.45), 2.035 (0.75), 2.042 (0.79), L1): 2.050 (0.83),2.056 (0.84), 2.063 (1.08), Rt = 1.16 2.070 (0.92), 2.076 (0.65), 2.084(0.55), min; MS 2.177 (0.48), 2.184 (0.73), 2.194 (0.96), (ESIpos):2.204 (0.93), 2.212 (0.89), 2.222 (0.61), m/z = 463 2.361 (0.44), 2.635(0.42), 2.784 (16.00), [M + H]⁺ 4.218 (0.41), 4.240 (1.35), 4.253(2.26), 4.260 (2.33), 4.273 (1.44), 4.289 (0.47), 5.276 (0.62), 5.288(1.38), 5.303 (1.35), 5.315 (0.58), 5.753 (1.80), 6.779 (2.82), 6.795(3.02), 6.899 (1.36), 6.913 (2.78), 6.928 (1.56), 7.147 (1.37), 7.161(2.32), 7.175 (1.13), 7.336 (2.58), 7.342 (1.47), 7.351 (3.50), 7.367(1.58), 7.434 (1.15), 7.440 (1.23), 7.450 (1.98), 7.456 (2.00), 7.465(1.00), 7.471 (0.96), 7.698 (2.97), 7.701 (2.98), 7.714 (4.43), 7.727(3.55), 7.729 (3.39), 7.757 (2.79), 7.773 (3.09), 7.788 (1.77), 8.296(2.65), 8.299 (2.73), 8.313 (2.51), 8.315 (2.43), 8.725 (3.78), 8.730(3.80), 9.066 (1.31), 9.073 (1.41), 9.083 (1.35), 9.089 (1.27). 554LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.040 (0.54), 2.049(0.56), 2.058 (0.59), L1): 2.066 (0.62), 2.075 (0.86), 2.084 (0.82), Rt= 1.11 2.199 (0.74), 2.211 (0.72), 2.221 (0.67), min; MS 2.791 (16.00),4.239 (1.25), 4.248 (1.18), (ESIpos): 4.258 (1.91), 4.266 (2.10), 4.281(1.17), m/z = 449 5.278 (0.52), 5.292 (1.15), 5.311 (1.17), [M + H]⁺5.326 (0.53), 5.754 (2.08), 6.782 (2.11), 6.802 (2.36), 6.902 (1.03),6.921 (2.23), 6.939 (1.30), 7.149 (1.12), 7.167 (1.84), 7.184 (0.89),7.228 (0.92), 7.240 (0.93), 7.250 (0.92), 7.346 (1.97), 7.365 (1.80),7.584 (0.41), 7.599 (0.74), 7.612 (0.76), 7.624 (0.74), 7.639 (0.41),7.779 (1.17), 7.798 (2.28), 7.818 (2.13), 7.853 (2.63), 7.868 (1.51),8.336 (2.03), 8.339 (2.04), 8.357 (1.93), 8.795 (6.37), 9.088 (1.87),9.109 (1.81). 555 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.008 (0.81), 0.008 (0.91), 1.235 (0.83), L1): 1.583 (5.80), 1.773(0.41), 1.790 (0.55), Rt = 1.11 1.800 (0.64), 2.756 (0.59), 2.782(0.54), min; MS 2.812 (0.68), 2.820 (0.83), 2.977 (16.00), (ESIpos):7.042 (0.46), 7.061 (1.18), 7.070 (0.71), m/z = 504 7.072 (0.72), 7.087(0.98), 7.090 (1.00), [M + H]⁺ 7.106 (0.45), 7.109 (0.43), 7.131 (0.52),7.150 (0.77), 7.502 (1.01), 7.520 (0.90), 7.610 (0.79), 7.628 (1.21),7.632 (1.38), 7.638 (10.75), 7.649 (1.14), 7.771 (1.14), 7.774 (1.26),7.789 (0.96), 7.792 (0.96), 8.202 (1.03), 8.205 (1.09), 8.223 (0.99),8.227 (0.96), 8.645 (3.75), 8.744 (1.76). 562 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.149 (0.58), −0.008 (5.47), 0.008 L1):(4.38), 0.146 (0.61), 1.235 (1.34), 2.036 Rt = 0.74 (1.59), 2.073(0.95), 2.159 (1.17), 2.172 min; MS (1.51), 2.183 (1.48), 2.193 (1.40),2.327 (ESIpos): (1.17), 2.366 (0.64), 2.523 (2.77), 2.670 m/z = 533(1.31), 2.710 (0.67), 3.996 (0.51), 4.032 [M + H]⁺ (9.72), 4.078 (0.42),4.203 (0.70), 4.243 (3.57), 4.252 (4.02), 4.267 (2.26), 4.285 (0.76),4.941 (4.22), 4.966 (2.98), 5.213 (0.97), 5.228 (2.18), 5.247 (2.17),5.261 (0.90), 5.754 (8.48), 6.780 (4.08), 6.800 (4.58), 6.885 (1.79),6.903 (3.77), 6.922 (2.20), 7.146 (2.20), 7.164 (3.60), 7.182 (1.68),7.304 (3.88), 7.322 (3.85), 7.353 (2.26), 7.415 (1.60), 7.427 (2.01),7.435 (2.80), 7.447 (3.08), 7.454 (1.54), 7.466 (1.53), 7.649 (1.29),7.666 (5.30), 7.676 (5.97), 7.684 (13.71), 7.689 (6.43), 7.705 (4.35),7.709 (4.08), 8.136 (4.77), 8.308 (0.72), 8.317 (3.74), 8.325 (3.26),8.334 (3.46), 8.342 (3.29), 8.630 (16.00), 8.707 (5.45), 9.196 (1.74),9.214 (2.90), 9.233 (1.90). 563 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.149 (1.20), −0.008 (9.34), 0.008 L1): (9.02), 0.146 (1.08),0.854 (0.58), 1.148 Rt = 0.85 (0.41), 1.235 (3.04), 2.039 (1.61), 2.085min; MS (3.50), 2.183 (1.52), 2.194 (1.37), 2.327 (ESIpos): (1.81),2.366 (0.93), 2.669 (2.04), 2.709 m/z = 567 (1.02), 3.508 (0.47), 4.039(9.81), 4.253 [M + H]⁺ (3.88), 4.268 (2.28), 4.948 (4.73), 4.972 (2.77),5.225 (2.25), 5.243 (2.22), 5.754 (7.04), 6.782 (4.76), 6.803 (5.23),6.888 (2.10), 6.907 (4.29), 6.925 (2.45), 7.149 (2.36), 7.167 (3.91),7.184 (1.96), 7.305 (3.50), 7.325 (3.18), 7.454 (2.39), 7.477 (2.69),7.483 (2.60), 7.652 (2.51), 7.670 (4.47), 7.691 (4.44), 7.721 (5.26),7.737 (2.92), 7.910 (8.35), 7.916 (8.23), 8.163 (2.04), 8.338 (4.35),8.341 (4.50), 8.359 (4.20), 8.362 (3.94), 8.642 (16.00), 8.717 (5.69),9.213 (2.63), 9.233 (2.51). 569 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (2.40), 0.008 (2.06), 2.061 (1.27), L1): 2.185 (1.12),2.327 (0.94), 2.669 (0.87), Rt = 0.78 4.025 (5.86), 4.065 (0.57), 4.238(1.84), min; MS 4.258 (2.64), 4.266 (2.99), 4.913 (1.72), (ESIpos):4.926 (3.39), 4.946 (3.52), 4.959 (1.75), m/z = 549 5.246 (1.74), 5.266(1.56), 6.792 (3.51), [M + H]⁺ 6.813 (3.85), 6.904 (1.66), 6.922 (3.36),6.939 (2.06), 7.158 (1.80), 7.175 (2.74), 7.197 (1.28), 7.321 (2.74),7.338 (2.56), 7.392 (1.86), 7.411 (2.11), 7.578 (2.92), 7.588 (4.18),7.597 (5.85), 7.616 (4.05), 7.627 (5.32), 7.647 (1.93), 7.652 (2.84),7.670 (3.21), 7.691 (2.98), 7.814 (3.61), 7.817 (3.83), 7.832 (3.05),8.291 (3.30), 8.310 (3.02), 8.706 (16.00), 9.217 (2.96), 9.237 (2.95).570 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (0.87),0.008 (0.82), 1.308 (6.89), L1): 1.327 (16.00), 1.345 (7.07), 2.024(0.53), Rt = 1.27 2.039 (1.21), 2.049 (1.28), 2.058 (1.29), min; MS2.066 (1.35), 2.075 (1.94), 2.083 (1.61), (ESIpos): 2.090 (1.19), 2.099(0.77), 2.180 (0.74), m/z = 493 2.190 (1.30), 2.203 (1.54), 2.213(1.54), [M + H]⁺ 2.225 (1.35), 2.243 (0.95), 2.256 (0.53), 3.233 (1.89),3.252 (5.94), 3.271 (5.86), 3.289 (1.97), 4.220 (0.46), 4.229 (0.69),4.249 (2.90), 4.258 (4.37), 4.268 (5.05), 4.275 (4.55), 4.284 (2.85),4.302 (0.68), 5.294 (1.14), 5.309 (2.53), 5.329 (2.56), 5.344 (1.15),6.785 (4.65), 6.805 (5.16), 6.910 (2.22), 6.913 (2.38), 6.931 (4.95),6.948 (2.88), 6.950 (2.91), 7.148 (2.35), 7.152 (2.57), 7.169 (4.01),7.187 (1.89), 7.190 (1.93), 7.348 (4.27), 7.366 (3.97), 7.402 (2.57),7.421 (3.07), 7.587 (3.08), 7.606 (10.61), 7.626 (5.62), 7.636 (4.50),7.639 (7.18), 7.658 (2.73), 7.756 (2.88), 7.774 (4.86), 7.795 (4.63),7.845 (5.60), 7.847 (6.27), 7.862 (3.86), 7.865 (3.83), 8.305 (4.57),8.324 (4.08), 8.326 (4.06), 8.800 (15.69), 9.096 (4.36), 9.117 (4.28).571 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.051 (0.52), 2.060(0.52), 2.087 (0.83), L1): 2.095 (0.71), 2.206 (0.69), 2.217 (0.69), Rt= 1.21 2.227 (0.59), 2.793 (16.00), 4.247 (1.21), min; MS 4266 (1.74),4.272 (1.87), 4.287 (1.09), (ESIpos): 5.288 (0.50), 5.303 (1.10), 5.323(1.10), m/z = 479 5.338 (0.49), 6.788 (2.15), 6.808 (2.34), [M + H]⁺6.911 (1.04), 6.927 (2.14), 6.946 (1.29), 7.154 (1.12), 7.171 (1.74),7.189 (0.83), 7.350 (1.84), 7.369 (1.70), 7.405 (1.21), 7.425 (1.42),7.591 (1.39), 7.610 (5.39), 7.629 (2.38), 7.646 (3.07), 7.665 (125),7.758 (1.35), 7.776 (2.19), 7.797 (2.04), 7.857 (2.46), 7.860 (2.60),7.875 (1.77), 7.878 (1.68), 8.268 (2.07), 8.271 (2.11), 8.289 (1.94),8.292 (1.85), 8.810 (6.83), 9.075 (1.81), 9.095 (1.79). 572 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 2.032 (0.65), 2.041 (0.71), 2.050(0.76), L1): 2.058 (0.79), 2.067 (1.04), 2.075 (0.91), Rt = 2.172(0.41), 2.181 (0.73), 2.193 (0.92), min; MS 2.204 (0.91), 2.215 (0.83),2.787 (16.00), (ESIpos): 4.216 (0.41), 4.236 (1.41), 4.254 (2.29), m/z =4.261 (2.58), 4.276 (1.47), 4.294 (0.44), [M + H]⁺ 5.271 (0.58), 5.286(1.35), 5.304 (1.38), 5.320 (0.61), 6.778 (2.39), 6.799 (2.67), 6.897(1.24), 6.915 (2.63), 6.934 (1.54), 7.145 (1.36), 7.163 (2.20), 7.184(1.05), 7.337 (2.34), 7.355 (2.19), 7.495 (2.29), 7.502 (1.52), 7.657(0.42), 7.771 (6.93), 7.779 (3.68), 7.787 (3.32), 7.805 (0.67), 7.922(2.71), 7.928 (2.67), 8.315 (1.92), 8.324 (1.81), 8.332 (1.66), 8.340(1.74), 8.751 (4.10), 9.078 (2.11), 9.099 (2.06). 573 LC-MS ¹H-NMR (400MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.08), 0.008 (1.69), 1.311(7.04), L1): 1.329 (16.00), 1.348 (7.23), 2.018 (1.23), Rt = 1.32 2.028(1.39), 2.037 (1.33), 2.053 (2.00), min; MS 2.062 (1.64), 2.188 (1.63),2.198 (1.61), (ESIpos): 2.210 (1.49), 2.229 (1.04), 2.241 (0.61), m/z =511 2.327 (0.71), 2.670 (0.76), 3.241 (3.86), [M + H]⁺ 3.260 (3.83),4.217 (0.70), 4.236 (2.98), 4.246 (4.20), 4.256 (5.08), 4.263 (4.65),4.272 (2.85), 4.290 (0.68), 5.274 (1.17), 5.289 (2.57), 5.308 (2.57),5.323 (1.14), 6.776 (5.42), 6.796 (5.89), 6.897 (2.61), 6.899 (2.58),6.915 (5.46), 6.934 (3.26), 7.140 (2.67), 7.144 (2.76), 7.161 (4.38),7.179 (2.11), 7.332 (4.46), 7.351 (4.10), 7.492 (4.02), 7.498 (7.24),7.504 (4.01), 7.755 (2.30), 7.767 (14.83), 7.772 (8.12), 7.785 (6.89),7.803 (1.92), 7.919 (10.30), 7.925 (9.81), 8.348 (4.00), 8.355 (3.95),8.367 (3.57), 8.373 (3.60), 8.742 (7.68), 8.747 (7.69), 9.108 (3.20),9.127 (3.19). 574 LC-MS ¹H-NMR (400 MHz DMSO-d6) δ [ppm]: (Method 1.196(5.36), 1.216 (11.90), 1.234 (5.37), L1): 2.071 (0.42), 2.613 (1.31),2.632 (3.68), Rt = 0.91 2.651 (3.53), 2.669 (1.23), 3.055 (16.00), min;MS 4.243 (0.61), 4.251 (0.57), 4.262 (0.88), (ESIpos): 4.270 (0.97),4.284 (0.51), 5.245 (0.56), m/z = 480 5.264 (0.54), 6.788 (1.10), 6.806(1.17), [M + H]⁺ 6.902 (0.54), 6.905 (0.53), 6.921 (1.09), 6.939 (0.67),6.942 (0.61), 7.064 (1.62), 7.148 (0.57), 7.152 (0.61), 7.169 (0.97),7.191 (3.92), 7.351 (0.92), 7.368 (0.83), 7.588 (0.68), 7.606 (1.18),7.626 (1.17), 7.657 (1.35), 7.661 (1.40), 7.675 (0.81), 7.679 (0.68),8.153 (1.09), 8.156 (1.06), 8.173 (0.99), 8.177 (0.92), 8.573 (4.21),9.076 (0.96), 9.096 (0.92). 575 LC-MS ¹H-NMR (400 MHz DMSO-d6) δ [ppm]:(Method 1.315 (7.37), 1.334 (16.00), 1.352 (7.13), L1): 2.016 (1.34),2.026 (1.38), 2.034 (1.42), Rt = 1.22 2.051 (2.04), 2.060 (1.67), 2.188(1.64), min; MS 2.210 (1.45), 2.224 (1.01), 2.327 (0.50), (ESIpos):2.669 (0.61), 3.238 (3.99), 3.257 (4.06), m/z = 477 4.245 (4.33), 4.256(5.35), 4.271 (2.97), [M + H]⁺ 5.276 (1.22), 5.290 (2.56), 5.309 (2.47),5.324 (1.11), 6.773 (5.14), 6.792 (5.52), 6.895 (2.45), 6.913 (5.11),6.932 (2.89), 7.141 (2.70), 7.159 (4.13), 7.176 (1.99), 7.330 (4.58),7.349 (6.16), 7.359 (3.61), 7.363 (4.57), 7.425 (2.86), 7.431 (3.07),7.444 (4.36), 7.451 (4.11), 7.464 (2.31), 7.470 (2.10), 7.693 (6.38),7.697 (6.72), 7.702 (4.33), 7.705 (4.53), 7.713 (6.16), 7.717 (7.18),7.719 (7.98), 7.723 (6.68), 7.752 (5.37), 7.772 (5.59), 7.790 (3.08),8.326 (4.48), 8.329 (4.58), 8.347 (4.17), 8.718 (7.77), 8.724 (7.76),9.099 (4.38), 9.120 (4.17). 582 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.161 (1.21), 1.180 (2.69), 1.196 (3.31), L1): 1.216 (3.24),1.230 (2.47), 1.235 (1.47), Rt = 0.99 1.249 (1.09), 1.356 (0.40), 2.044(0.41), min; MS 2.184 (0.41), 2.595 (0.99), 2.609 (1.17), (ESIpos):2.628 (1.01), 2.728 (0.96), 2.745 (1.23), m/z = 514 2.763 (0.79), 3.065(16.00), 4.229 (0.62), [M + H]⁺ 4.237 (0.58), 4.248 (0.91), 4.256(1.04), 4.270 (0.58), 5.227 (0.48), 5.241 (0.48), 6.774 (1.04), 6.794(1.15), 6.883 (0.48), 6.902 (1.01), 6.920 (0.59), 6.967 (0.72), 6.972(0.72), 6.996 (0.74), 7.001 (0.75), 7.138 (0.56), 7.156 (0.90), 7.174(0.45), 7.218 (1.64), 7.223 (1.57), 7.331 (0.76), 7.350 (0.71), 7.550(0.70), 7.567 (1.32), 7.595 (1.22), 7.616 (1.30), 7.633 (0.71), 8.199(1.07), 8.203 (1.13), 8.220 (1.01), 8.224 (1.00), 8.506 (2.86), 9.055(0.47), 9.073 (0.74), 9.092 (0.49). 583 LC-MS ¹H-NMR (400 MHz, DMSO-d6)δ [ppm]: (Method 0.008 (1.62), 1.142 (0.89), 1.161 (6.60), L1): 1.180(13.02), 1.195 (16.00), 1.216 Rt = 1.20 (15.26), 1.229 (11.19), 1.234(6.42), 1.248 min; MS (5.03), 1.356 (2.57), 2.034 (1.17), 2.061(ESIpos): (1.72), 2.182 (1.53), 2.194 (1.58), 2.207 m/z = 556 (1.56),2.217 (1.57), 2.327 (0.56), 2.366 [M + H]⁺ (0.40), 2.578 (1.59), 2.596(4.14), 2.610 (4.95), 2.629 (4.33), 2.648 (1.32), 2.709 (1.71), 2.728(3.88), 2.745 (4.90), 2.763 (3.19), 3.875 (11.89), 4.211 (0.84), 4.232(2.57), 4.252 (3.80), 4.262 (3.67), 4.279 (2.36), 5.242 (2.14), 5.256(2.13), 6.776 (4.90), 6.796 (5.51), 6.892 (1.72), 6.910 (3.66), 6.929(2.06), 6.969 (3.24), 6.974 (3.27), 7.000 (3.63), 7.005 (3.58), 7.141(2.39), 7.161 (3.89), 7.180 (2.02), 7.225 (7.39), 7.230 (6.95), 7.352(4.16), 7.370 (3.84), 7.591 (3.42), 7.607 (5.69), 7.646 (5.21), 7.667(5.45), 7.685 (3.27), 8.243 (4.62), 8.246 (4.72), 8.263 (4.30), 8.267(4.07), 8.566 (8.87), 8.571 (9.34), 9.136 (2.13), 9.154 (3.49), 9.173(2.18). 585 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm] (Method −0.008(0.77), 0.008 (0.70), 2.009 (0.45), L4): 2.124 (0.42), 2.137 (0.56),2.159 (0.67), Rt = 3.93 2.173 (0.54), 2.729 (16.00), 3.132 (8.33), min;MS 3.140 (9.59), 4.242 (1.09), 4.256 (1.79), (ESIpos): 4.268 (1.30),4.285 (0.74), 4.304 (0.47), m/z = 520 4.313 (0.51), 5.228 (0.59), 5.244(0.74), [M + H]⁺ 5.261 (0.70), 5.277 (0.49), 5.754 (5.28), 6.788 (0.97),6.800 (1.15), 6.807 (1.12), 6.818 (1.26), 6.861 (0.47), 6.879 (1.00),6.898 (0.64), 6.905 (0.63), 6.923 (1.16), 6.942 (0.70), 7.145 (0.53),7.163 (1.32), 7.184 (1.31), 7.201 (1.14), 7.217 (0.79), 7.322 (0.99),7.341 (0.88), 7.673 (1.37), 7.677 (3.00), 7.682 (2.18), 7.707 (7.29),7.712 (5.77), 7.789 (0.70), 7.809 (2.12), 7.827 (3.94), 7.832 (2.99),7.849 (0.62), 7.852 (0.68), 7.975 (1.92), 7.980 (1.72), 7.991 (1.71),7.996 (1.45), 9.158 (4.20), 9.183 (4.34), 9.199 (1.01). 586 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 1.313 (16.00), 2.359 (3.34), 3.056(5.98), L1): 4.262 (0.45), 4.271 (0.52), 6.788 (0.52), Rt = 0.98 6.809(0.57), 6.924 (0.54), 7.173 (1.16), min; MS 7.218 (0.69), 7.346 (0.96),7.367 (0.45), (ESIpos): 7.611 (0.52), 7.631 (0.52), 7.659 (0.59), m/z =494 8.157 (0.42), 8.564 (1.24), 9.083 (0.42), [M + H]⁺ 9.103 (0.42). 587LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 1.295 (2.20), 1.313(16.00), 2.360 (4.01), L1): 3.276 (1.42), 3.287 (1.54), 3.875 (2.03), Rt= 1.18 4.268 (0.54), 6.789 (0.67), 6.810 (0.75), min; MS 6.932 (0.71),6.950 (0.41), 7.156 (0.40), (ESIpos): 7.175 (1.57), 7.225 (0.98), 7.349(1.06), m/z = 536 7.373 (0.71), 7.392 (0.66), 7.659 (0.78), [M + H]⁺7.679 (0.75), 7.698 (0.86), 7.712 (0.44), 8.213 (0.58), 8.230 (0.53),8.623 (1.85), 9.157 (0.60), 9.178 (0.59). 588 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.008 (1.01), 0.008 (0.99), 1.197 (7.08),L1): 1.216 (16.00), 1.234 (7.43), 2.089 (0.55), Rt = 1.14 2.096 (0.46),2.208 (0.52), 2.220 (0.48), min; MS 2.230 (0.47), 2.327 (0.44), 2.522(1.17), (ESIpos): 2.615 (1.76), 2.634 (5.17), 2.653 (5.02), m/z = 5222.671 (1.92), 3.243 (0.45), 3.262 (1.26), [M + H]⁺ 3.275 (2.62), 3.287(2.82), 3.874 (4.06), 4.245 (0.80), 4.253 (0.63), 4.267 (1.07), 4.277(1.01), 4.293 (0.68), 5.259 (0.75), 5.278 (0.75), 5.754 (1.39), 6.789(1.42), 6.810 (1.58), 6.913 (0.73), 6.932 (1.50), 6.948 (0.89), 6.951(0.88), 7.073 (2.20), 7.152 (0.74), 7.156 (0.80), 7.173 (1.25), 7.194(5.31), 7.373 (1.25), 7.391 (1.18), 7.638 (0.84), 7.656 (1.64), 7.676(1.69), 7.695 (1.79), 7.699 (2.07), 7.713 (0.99), 7.717 (0.85), 8.208(1.34), 8.212 (1.38), 8.229 (126), 8.233 (1.22), 8.629 (5.50), 9.153(1.39), 9.173 (1.34). 592 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]:(Method 1.234 (0.47), 2.106 (0.61), 2.117 (0.70), L1): 2.129 (0.79),2.134 (0.71), 2.262 (0.49), Rt = 1.14 2.273 (0.68), 2.283 (0.72), 2.290(0.70), min; MS 2.301 (0.52), 4.035 (0.41), 4.195 (0.49), (ESIpos):4.200 (0.56), 4.218 (1.25), 4.235 (0.87), m/z = 479 4.240 (0.70), 4.289(0.70), 4.295 (0.92), [M + H]⁺ 4.301 (0.85), 4.308 (0.93), 4.318 (0.57),4.323 (0.56), 4.330 (0.43), 4.742 (1.91), 5.390 (0.52), 5.400 (1.12),5.416 (1.11), 5.427 (0.51), 5.554 (0.98), 6.793 (2.09), 6.808 (2.27),6.937 (1.02), 6.952 (2.13), 6.966 (1.23), 7.163 (1.03), 7.166 (1.07),7.180 (1.76), 7.194 (0.87), 7.197 (0.82), 7.410 (1.80), 7.424 (1.69),7.665 (16.00), 7.737 (1.30), 7.752 (2.11), 7.768 (1.83), 7.845 (2.28),7.848 (2.39), 7.860 (1.82), 7.862 (1.73), 7.967 (1.51), 7.984 (1.29),8.488 (0.66), 9.045 (5.88), 9.260 (1.85), 9.277 (1.82). 593 1.18 min;¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: MS 1.190 (0.46), 2.062 (0.53), 2.068(0.53), (ESIpos): 2.076 (0.53), 2.090 (0.66), 2.096 (0.59), m/z = 4932.213 (0.59), 2.223 (0.59), 2.230 (0.53), [M + H]⁺ 2.362 (0.53), 2.519(0.72), 2.522 (0.53), 2.636 (0.53), 3.460 (0.99), 3.473 (2.24), 3.487(1.32), 3.780 (1.05), 3.790 (1.51), 3.799 (0.99), 4.230 (0.46), 4.246(1.12), 4.253 (0.79), 4.263 (1.05), 4.268 (1.32), 4.275 (0.99), 4.281(0.79), 4.288 (0.86), 5.091 (0.86), 5.101 (1.78), 5.111 (0.79), 5.286(0.40), 5.297 (0.86), 5.314 (0.86), 6.786 (1.91), 6.789 (1.91), 6.803(2.17), 6.805 (2.11), 6.906 (1.05), 6.908 (1.12), 6.921 (1.91), 6.923(1.84), 6.935 (1.19), 6.938 (1.12), 7.153 (0.99), 7.156 (0.99), 7.170(1.51), 7.184 (0.79), 7.352 (1.12), 7.359 (1.58), 7.374 (1.38), 7.537(0.40), 7.648 (4.54), 7.651 (16.00), 7.654 (3.23), 7.659 (0.72), 7.693(0.66), 7.754 (1.45), 7.769 (1.91), 7.771 (1.65), 7.786 (1.78), 7.877(2.17), 7.880 (2.24), 7.891 (1.78), 7.894 (1.65), 8.359 (1.58), 8.362(1.65), 8.377 (1.58), 8.869 (7.57), 9.225 (1.65), 9.242 (1.58). 594LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.050 (0.60), 2.058(0.65), 2.069 (0.70), L1): 2.085 (0.97), 2.092 (0.83), 2.100 (0.60), Rt= 1.04 2.197 (0.65), 2.209 (0.88), 2.221 (0.86), min; MS 2.230 (0.81),2.243 (0.56), 2.252 (0.44), (ESIpos): 2.327 (0.42), 2.429 (16.00), 2.670(0.44), m/z = 505 3.252 (0.90), 3.272 (2.69), 3.283 (5.98), [M + H]⁺3.295 (7.10), 3.867 (4.41), 3.878 (7.26), 3.889 (4.17), 4.224 (0.46),4.245 (1.41), 4.252 (1.14), 4.266 (1.97), 4.275 (1.86), 4.292 (1.23),4.311 (0.44), 5.243 (0.60), 5.257 (1.32), 5.276 (1.32), 5290 (0.58),6.788 (2.37), 6.809 (2.62), 6.914 (1.18), 6.916 (1.21), 6.933 (2.50),6.951 (1.48), 7.153 (1.23), 7.156 (1.30), 7.174 (2.09), 7.192 (1.02),7.195 (1.00), 7.376 (2.23), 7.394 (2.09), 7.685 (3.87), 7.702 (2.60),7.723 (2.30), 7.741 (3.73), 7.802 (2.78), 7.805 (2.92), 7.820 (2.32),7.823 (2.62), 7.831 (3.66), 8.267 (2.32), 8.270 (2.39), 8.288 (2.20),8.291 (2.13), 8.679 (8.26), 9.161 (2.34), 9.182 (2.30). 598 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (0.75), 0.008 (0.48), 2.068(0.58), L1): 2.076 (0.47), 2.175 (0.42), 2.188 (0.51), Rt = 0.84 2.199(0.49), 2.209 (0.45), 2.427 (9.40), min; MS 2.523 (1.01), 3.070 (16.00),4.242 (0.87), (ESIpos): 4.250 (0.80), 4.261 (1.24), 4.269 (1.37), m/z =463 4.284 (0.72), 5.241 (0.79), 5.261 (0.75), [M + H]⁺ 6.785 (1.39),6.787 (1.45), 6.805 (1.56), 6.808 (1.54), 6.905 (0.76), 6.908 (0.76),6.924 (1.51), 6.926 (1.43), 6.942 (0.91), 6.945 (0.84), 7.149 (0.77),7.153 (0.79), 7.170 (1.19), 7.187 (0.59), 7.191 (0.55), 7.354 (1.25),7.372 (1.15), 7.632 (1.11), 7.650 (1.59), 7.654 (1.36), 7.672 (1.79),7.680 (1.98), 7.737 (2.19), 7.739 (2.19), 7.762 (1.69), 7.766 (1.74),7.780 (1.33), 7.783 (1.21), 7.828 (2.17), 8.220 (1.41), 8.223 (1.38),8.241 (1.29), 8.244 (1.19), 8.613 (3.96), 9.082 (1.26), 9.103 (1.19).600 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method 2.033 (0.49), 2.041(0.52), 2.068 (0.76), L1): 2.076 (0.68), 2.195 (0.64), 2.205 (0.65), Rt= 1.13 2.216 (0.57), 2.783 (16.00), 4.236 (1.14), min; MS 4.255 (1.65),4.262 (1.79), 4.276 (1.08), (ESIpos): 5.274 (0.47), 5.288 (1.06), 5.308(1.05), m/z = 447 5.323 (0.49), 6.778 (2.06), 6.799 (2.26), [M + H]⁺6.898 (1.00), 6.914 (2.08), 6.933 (1.25), 7.141 (1.01), 7.145 (1.08),7.163 (1.66), 7.180 (0.81), 7.266 (1.14), 7.274 (1.67), 7.289 (1.20),7.296 (1.69), 7.303 (1.14), 7.311 (0.77), 7.324 (1.88), 7.333 (2.15),7.345 (1.33), 7.354 (2.23), 7.584 (1.59), 7.597 (1.64), 7.606 (1.48),7.619 (1.41), 7.717 (1.13), 7.720 (1.36), 7.734 (2.93), 7.738 (2.68),7.753 (2.46), 7.773 (2.49), 7.791 (1.20), 8.293 (1.91), 8.297 (2.02),8.314 (1.85), 8.318 (1.75), 8.738 (6.49), 9.072 (1.70), 9.093 (1.64).601 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (0.79),0.008 (0.75), 1.270 (12.17), L1): 1.284 (12.89), 2.388 (3.41), 2.401 Rt= 1.01 (3.26), 2.523 (0.94), 3.065 (16.00), 4.232 min; MS (0.55), 4.245(0.88), 4.255 (1.03), 4.270 (ESIpos): (0.61), 5.224 (0.60), 5.243(0.60), 5.754 m/z = 528 (1.14), 6.774 (1.15), 6.795 (1.28), 6.885 [M +H]⁺ (0.58), 6.903 (1.22), 6.922 (0.69), 7.096 (0.63), 7.102 (0.70),7.123 (0.72), 7.128 (0.75), 7.135 (0.65), 7.139 (0.65), 7.156 (0.97),7.178 (0.46), 7.331 (0.94), 7.350 (0.87), 7.411 (1.63), 7.416 (1.58),7.550 (0.92), 7.565 (1.38), 7.601 (1.33), 7.621 (1.46), 7.639 (0.85),8.203 (1.13), 8.206 (1.22), 8.224 (1.07), 8.228 (1.06), 8.503 (1.65),8.508 (1.79), 9.069 (1.03), 9.089 (1.02). 602 LC-MS ¹H-NMR (400 MHz,DMSO-d6) δ [ppm]: (Method −0.008 (2.43), 0.008 (2.43), 2.005 (1.56),L1): 2.014 (1.65), 2.040 (2.57), 2.048 (2.04), Rt = 0.72 2.174 (2.09),2.186 (2.16), 2.196 (2.02), min; MS 2.327 (0.80), 2.366 (0.85), 2.669(0.73), (ESIpos): 2.710 (0.83), 4.032 (11.82), 4.207 (1.19), m/z = 5174.227 (3.60), 4.235 (3.19), 4.246 (5.44), [M + H]⁺ 4.254 (6.06), 4.270(3.19), 4.287 (1.12), 4.938 (5.67), 4.956 (5.44), 5.217 (1.58), 5.231(3.35), 5.251 (3.28), 5.265 (1.40), 6.782 (6.82), 6.803 (7.51), 6.889(3.33), 6.907 (6.61), 6.924 (4.02), 7.145 (3.35), 7.149 (3.63), 7.166(5.42), 7.187 (2.64), 7.252 (2.89), 7.274 (2.87), 7.293 (2.71), 7.307(6.36), 7.314 (5.28), 7.323 (7.92), 7.335 (2.94), 7.343 (2.32), 7.576(3.70), 7.589 (4.11), 7.598 (3.56), 7.611 (3.28), 7.650 (2.62), 7.667(7.67), 7.686 (13.61), 7.701 (2.46), 8.132 (3.35), 8.319 (5.26), 8.325(4.96), 8.338 (4.77), 8.344 (4.55), 8.642 (16.00), 8.708 (6.38 9.213(4.73), 9.234 (4.61). 603 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.312 (7.07), 1.330 (16.00), 1.349 (7.30), L1): 2.004 (0.55),2.019 (1.26), 2.030 (1.33), Rt = 1.20 2.038 (1.35), 2. (347 (1.47),2.055 (2.00), min; MS 2.063 (1.72), 2.071 (1.26), 2.079 (0.81),(ESIpos): 2.167 (0.77), 2.178 (1.39), 2.190 (1.60), m/z = 461 2.200(1.63), 2.212 (1.45), 2.226 (1.03), [M + H]⁺ 2.243 (0.57), 3.220 (1.71),3.238 (4.68), 3.256 (4.64), 3.274 (1.72), 4.218 (0.71), 4.237 (3.03),4.246 (4.63), 4.256 (5.41), 4.263 (4.80), 4.272 (3.05), 4.291 (0.73),5.278 (1.19), 5.293 (2.62), 5.312 (2.65), 5.328 (1.20), 6.775 (4.64),6.795 (5.15), 6.897 (2.35), 6.900 (2.37), 6.916 (5.03), 6.934 (3.02),7.139 (2.49), 7.143 (2.59), 7.160 (4.16), 7.178 (2.02), 7.181 (1.96),7.269 (2.88), 7.276 (4.09), 7.292 (3.57), 7.299 (6.76), 7.307 (2.30),7.321 (4.84), 7.330 (5.77), 7.342 (3.34), 7.350 (5.55), 7.436 (0.55),7.444 (0.73), 7.460 (2.03), 7.470 (1.50), 7.483 (0.63), 7.488 (0.63),7.582 (3.46), 7.595 (3.67), 7.604 (3.36), 7.617 (3.13), 7.635 (0.42),7.708 (2.96), 7.712 (3.38), 7.726 (6.55), 7.729 (6.17), 7.751 (5.10),7.772 (5.47), 7.790 (2.85), 8.326 (4.37), 8.329 (4.51), 8.347 (4.16),8.350 (4.04), 8.731 (14.58), 9.104 (4.09), 9.124 (3.99). 604 LC-MS¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (3.57), 0.008 (3.20),2.011 (1.02), L1): 2.020 (1.09), 2.046 (1.71), 2.054 (1.42), Rt = 0.762.167 (1.15), 2.178 (1.46), 2.189 (1.42), min; MS 2.200 (1.38), 2.327(1.33), 2.366 (0.84), (ESIpos): 2.523 (2.88), 2.669 (1.31), 2.710(0.80), m/z = 517 3.998 (0.69), 4.038 (7.81), 4.078 (0.67), [M + H]⁺4.210 (0.82), 4.230 (2.51), 4.238 (2.22), 4.249 (3.71), 4.258 (4.19),4.272 (2.17), 4.927 (2.42), 4.940 (4.59), 4.963 (4.55), 4.975 (2.31),5.221 (1.04), 5.234 (2.24), 5.255 (2.20), 5.268 (0.95), 6.785 (4.62),6.806 (4.88), 6.892 (2.31), 6.911 (4.53), 6.929 (2.71), 6.954 (0.51),6.961 (0.47), 6.974 (0.51), 6.980 (0.47), 7.149 (2.60), 7.170 (3.77),7.187 (1.84), 7.191 (1.80), 7.200 (0.51), 7.313 (4.11), 7.320 (3.57),7.330 (3.82), 7.342 (6.10), 7.365 (3.68), 7.486 (3.11), 7.493 (4.44),7.502 (3.13), 7.508 (4.84), 7.522 (3.02), 7.529 (1.75), 7.533 (2.37),7.540 (1.93), 7.544 (2.24), 7.551 (1.58), 7.650 (3.11), 7.667 (4.50),7.671 (3.77), 7.688 (4.24), 7.776 (4.79), 7.791 (3.62), 8.133 (0.44),8.323 (4.42), 8.326 (4.28), 8.344 (4.04), 8.347 (3.75), 8.661 (16.00),8.710 (5.68 9.208 (3.97), 9.228 (3.79), 10.355 (1.09). 605 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 2.038 (0.55), 2.048 (0.59), 2.057(0.62), L1): 2.064 (0.65), 2.074 (0.89), 2.082 (0.75), Rt = 1.16 2.089(0.55), 2.185 (0.61), 2.197 (0.74), min; MS 2.209 (0.73), 2.219 (0.68),2.787 (16.00), (ESIpos): 4.239 (1.30), 4.248 (1.30), 4.258 (1.93), m/z =447 4.265 (2.14), 4.279 (1.20), 5.277 (0.53), [M + H]⁺ 5.292 (1.20),5.311 (1.21), 5.326 (0.54), 6.780 (2.05), 6.800 (2.32), 6.901 (1.05),6.920 (2.28), 6.938 (1.33), 7.148 (1.14), 7.166 (1.88), 7.183 (0.88),7.333 (1.49), 7.343 (2.14), 7.356 (3.17), 7.378 (1.66), 7.505 (1.11),7.511 (1.81), 7.526 (2.33), 7.534 (1.46), 7.545 (1.03), 7.556 (1.03),7.562 (0.70), 7.757 (1.11), 7.776 (2.36), 7.796 (2.24), 7.821 (2.68),7.836 (1.38), 8.304 (2.03), 8.325 (1.92), 8.769 (6.05), 9.077 (1.92),9.097 (1.89). 607 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: (Method−0.149 (0.48), −0.008 (3.63), 0.008 L1): (3.53), 0.146 (0.46), 1.175(0.42), 1.269 Rt = 1.26 (14.91), 1.283 (16.00), 1.398 (0.57), min; MS1.988 (0.79), 2.065 (0.44), 2.195 (0.48), (ESIpos): 2.327 (0.69), 2.366(0.79), 2.388 (4.14), m/z = 570 2.401 (3.93), 2.669 (0.75), 2.709(0.77), [M + H]⁺ 3.283 (1.88), 3.876 (3.43), 4.231 (0.63), 4.252 (1.03),4.279 (0.69), 5.238 (0.73), 5.258 (0.77), 5.754 (0.79), 6.776 (1.43),6.797 (1.53), 6.891 (0.65), 6.910 (1.35), 6.928 (0.81), 7.102 (0.85),7.131 (0.91), 7.143 (0.77), 7.161 (1.15), 7.180 (0.54), 7.353 (1.27),7.370 (1.19), 7.418 (2.00), 7.424 (1.98), 7.590 (1.03), 7.607 (1.61),7.652 (1.47), 7.673 (1.61), 7.690 (1.01), 8.250 (1.37), 8.267 (1.23),8.564 (1.86), 8.572 (2.04), 9.148 (1.21), 9.168 (1.17). 608 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method −0.008 (2.94), 0.008 (2.84), 2.026(1.36), L1): 2.034 (1.46), 2.045 (1.57), 2.061 (2.14), Rt = 1.12 2.068(1.86), 2.076 (1.39), 2.183 (1.38), min; MS 2.196 (1.99), 2.207 (1.94),2.217 (1.90), (ESIpos): 2.230 (1.30), 2.252 (0.65), 2.327 (0.62), m/z =559 2.366 (0.58), 2.669 (0.72), 2.710 (0.61), [M + H]⁺ 3.254 (1.39),3.294 (9.84), 3.879 (15.30), 4.202 (0.81), 4.209 (1.06), 4.230 (3.23),4.238 (2.57), 4.251 (4.00), 4.263 (3.86), 4.279 (2.90), 4.298 (1.09),4.306 (0.75), 5.239 (2.49), 5.253 (2.51), 5.754 (2.12), 6.778 (5.59),6.798 (6.16), 6.895 (2.42), 6.913 (5.26), 6.932 (3.13), 7.142 (2.78),7.146 (3.03), 7.164 (4.72), 7.181 (2.33), 7.185 (2.30), 7.354 (5.00),7.372 (4.65), 7.706 (2.07), 7.724 (7.43), 7.737 (7.97), 7.742 (16.00),7.754 (2.22), 7.885 (2.90), 7.892 (3.07), 7.917 (3.30), 7.921 (3.26),8.052 (0.43), 8.297 (0.70), 8.310 (4.84), 8.316 (4.51), 8.328 (4.39),8.334 (4.48), 8.342 (7.65), 8.347 (7.65), 8.604 (10.28), 8.706 (0.70),9.165 (3.36), 9.184 (3.22). 624 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method −0.008 (1.20), 0.008 (1.22), 2.044 (0.43), L1): 2.185 (0.41),2.195 (0.40), 3.080 (16.00), Rt = 0.97 4.227 (0.67), 4.246 (1.04), 4.254(1.15), min; MS 4.269 (0.62), 5.235 (0.51), 5.754 (3.68), (ESIpos):6.776 (1.33), 6.796 (1.47), 6.887 (0.57), m/z = 517 6.905 (1.24), 6.924(0.75), 7.142 (0.65), [M + H]⁺ 7.159 (1.03), 7.180 (0.52), 7.331 (0.80),7.350 (0.73), 7.652 (0.64), 7.670 (1.58), 7.690 (2.46), 7.697 (1.81),7.710 (0.61), 7.882 (0.81), 7.908 (0.84), 8.278 (1.17), 8.283 (1.16),8.298 (1.11), 8.303 (1.04), 8.333 (2.42), 8.337 (2.34), 8.531 (4.40),9.078 (0.75), 9.098 (0.70). 628 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]:(Method 1.308 (7.60), 1.326 (16.00), 1.345 (7.79), L1): 2.061 (2.32),2.203 (2.13), 2.327 (0.52), Rt = 1.22 2.670 (0.63), 3.243 (6.84), 3.262(6.74), min; MS 3.280 (2.77), 4.260 (6.66), 5.298 (3.26), (ESIpos):5.314 (3.18), 6.777 (5.35), 6.797 (5.91), m/z = 461 6.903 (2.66), 6.921(5.56), 6.940 (3.25), [M + H]⁺ 7.145 (3.07), 7.163 (4.94), 7.182 (2.42),7.339 (6.05), 7.354 (9.10), 7.375 (3.63), 7.511 (5.22), 7.526 (7.31),7.550 (2.82), 7.756 (2.29), 7.774 (5.35), 7.794 (5.18), 7.810 (7.32),7.827 (3.38), 8.338 (4.91), 8.358 (4.55), 8.763 (13.33), 9.106 (4.65),9.126 (4.63). 631 LC-MS ¹H-NMR (400 MHz, DMSO-d6) δ [ppm] (Method 1.091(0.41), 1.235 (1.08), 1.259 (0.68), L1): 1.299 (0.43), 2.066 (16.00),2.100 (0.88), Rt = 3.90 2.214 (0.78), 2.226 (0.77), 2.235 (0.72), min;MS 2.268 (1.76), 2.328 (0.58), 2.669 (0.60), (ESIpos): 2.750 (15.89),4.208 (0.55), 4.228 (1.45), m/z = 534 4.249 (1.16), 4.258 (1.27), 4.269(1.15), [M + H]⁺ 4.286 (1.02), 5.143 (5.73), 5.250 (0.77), 5.282 (1.13),5.301 (1.12), 6.790 (2.18), 6.810 (2.37), 6.917 (1.17), 6.935 (2.21),6.953 (1.25), 7.157 (1.18), 7.177 (1.96), 7.195 (0.95), 7.381 (1.90),7.400 (1.94), 7.654 (11.00), 7.658 (5.85), 7.723 (1.28), 7.741 (1.94),7.762 (1.68), 7.882 (2.40), 7.898 (1.87), 8.251 (2.03), 8.270 (1.81),8.917 (0.60), 8.948 (6.71), 9.278 (1.90), 9.298 (1.82). 643 LC-MS ¹H-NMR(400 MHz, DMSO-d6) δ [ppm]: (Method 0.008 (0.88), 2.089 (0.52), 2.238(16.00), L1): 2.669 (1.25), 3.317 (2.60), 3.422 (1.31), Rt = 0.91 3.438(1.42), 3.460 (1.08), 4.250 (0.72), min; MS 4.269 (1.14), 4.278 (1.25),4.293 (0.65), (ESIpos): 5.290 (0.69), 5.310 (0.69), 5.754 (0.94), m/z =520 6.792 (1.36), 6.812 (1.48), 6.900 (0.70), [M + H]⁺ 6.919 (1.32),6.937 (0.81), 7.158 (0.66), 7.175 (1.10), 7.193 (0.52), 7.366 (1.17),7.383 (1.06), 7.654 (11.60), 7.771 (0.81), 7.789 (1.28), 7.810 (1.17),7.885 (1.61), 7.900 (1.17), 8.145 (3.08), 8.283 (1.19), 8.302 (1.09),8.871 (4.70), 9.325 (1.18), 9.345 (1.13). 645 LC-MS ¹H-NMR (500 MHz,DMSO-d6) δ [ppm]: (Method 2.039 (0.59), 2.046 (0.63), 2.054 (0.65), L1):2.059 (0.66), 2.067 (0.88), 2.072 (1.06), Rt = 1.18 2.080 (0.51), 2.186(0.59), 2.196 (0.76), min; MS 2.205 (0.79), 2.212 (0.72), 2.224 (0.47),(ESIpos): 2.229 (0.41), 2.335 (10.23), 2.779 m/z = 443 (16.00), 4.223(0.40), 4.239 (1.31), 4.246 [M + H]⁺ (1.16), 4.254 (2.05), 4.261 (2.12),4.274 (1.15), 5.280 (0.52), 5.292 (1.13), 5.307 (1.10), 5.319 (0.50),6.780 (2.18), 6.795 (2.35), 6.900 (1.09), 6.901 (1.08), 6.915 (2.22),6.929 (1.29), 6.931 (1.20), 7.145 (1.11), 7.147 (1.14), 7.161 (1.96),7.176 (3.03), 7.178 (3.05), 7.239 (1.53), 7.242 (1.36), 7.255 (1.82),7.258 (1.60), 7.338 (1.91), 7.353 (1.78), 7.411 (2.22), 7.427 (1.81),7.663 (1.80), 7.666 (1.84), 7.677 (2.62), 7.680 (2.49), 7.731 (2.08),7.746 (1.86), 7.748 (2.32), 7.762 (1.51), 8.260 (2.18), 8.262 (2.20),8.277 (2.05), 8.279 (1.93), 8.716 (5.69), 9.065 (1.86), 9.082 (1.80).646 LC-MS ¹H-NMR (500 MHz, DMSO-d6): δ (Method [ppm] = 9.10 (br d, 1H),8.71 (s, 1H), L1): 8.30 (d, 1H), 7.75 (t, 1H), 7.66 (d, 1H), Rt = 1.247.42 (d, 1H), 7.34 (d, 1H), 7.25 (dd, min; MS 1H), 7.19-7.14 (m, 2H),6.92 (t, 1H), (ESIpos): 6.78 (d, 1H), 5.33-5.28 (m, 1H), 4.29- m/z = 4574.22 (m, 2H), 3.36 (br s, 1H), 3.28-3.20 [M + H]⁺ (m, 2H), 2.33 (s, 3H),2.27-2.16 (m, 1H), 2.05 (ddd, 1H), 1.33 (t, 3H) 653 LC-MS ¹H-NMR (500MHz, DMSO-d6) δ [ppm]: (Method 1.160 (0.41), 1.175 (1.01), 1.189 (0.61),L1): 1.235 (0.61), 1.397 (2.84), 1.988 (3.65), Rt = 1.20 2.004 (2.63),2.085 (7.09), 2.155 (2.63), min; MS 2.165 (2.63), 2.172 (2.43), 2.362(1.01), (ESIpos): 2.432 (3.04), 2.636 (0.81), 3.375 (0.61), m/z = 5313.904 (2.23), 4.023 (0.61), 4.037 (0.61), [M + H]⁺ 4.219 (4.46), 4.242(6.08), 4.249 (6.08), 4.256 (5.47), 4.263 (5.87), 4.278 (3.24), 5.233(3.44), 5.247 (3.44), 5.752 (2.23), 5.856 (5.06), 6.764 (9.32), 6.766(9.72), 6.780 (10.33), 6.782 (10.33), 6.888 (2.84), 6.902 (5.87), 6.918(3.24), 7.138 (4.25), 7.141 (4.46), 7.155 (7.29), 7.169 (3.65), 7.334(6.08), 7.349 (6.48), 7.375 (4.46), 7.441 (3.85), 7.447 (4.46), 7.457(6.48), 7.463 (6.89), 7.472 (3.24), 7.478 (3.44), 7.708 (11.75), 7.711(11.75), 7.724 (15.39), 7.728 (16.00), 7.738 (14.38), 7.742 (12.96),7.751 (12.76), 7.767 (12.35), 7.781 (5.67), 8.059 (9.11), 8.062 (9.11),8.075 (7.90), 8.078 (7.49), 8.819 (13.57), 8.827 (13.57), 8.933 (5.27),8.949 (4.25). 654 LC-MS ¹H-NMR (500 MHz, CHLOROFORM-d) (Method δ [ppm]:0.006 (1.86), 1.222 (0.43), L1): 1.255 (1.78), 1.549 (4.29), 2.005(0.63), Rt = 1.17 2.009 (0.62), 2.025 (0.45), 2.034 (0.78), min; MS2.038 (0.71), 2.170 (2.80), 2.175 (0.46), (ESIpos): 2.270 (0.45), 2.281(0.47), 2.285 (0.45), m/z = 587 2.292 (0.67), 2.302 (0.60), 3.056(15.99), [M + H]⁺ 3.423 (4.44), 3.459 (16.00, 3.534 (4.30), 4.074(0.85), 4.079 (0.78), 4.097 (1.34), 4.101 (1.18), 4.119 (0.75), 4.124(0.61), 4.294 (0.63), 4.302 (1.10), 4.311 (0.65), 4.317 (0.54), 4.325(0.84), 4.333 (0.42), 5.348 (0.49), 5.358 (0.84), 5.367 (0.90), 5.375(0.81), 5.385 (0.43), 6.731 (0.89), 6.733 (0.88), 6.746 (1.75), 6.760(1.01), 6.762 (0.97), 6.823 (2.09), 6.840 (2.28), 6.922 (0.50), 7.080(1.31), 7.092 (1.92), 7.099 (1.43), 7.105 (1.69), 7.178 (1.13), 7.181(0.97), 7.195 (1.67), 7.209 (1.14), 7.212 (1.11), 7.220 (5.56), 7.282(0.46), 7.376 (1.54), 7.423 (2.79), 7.427 (3.79), 7.430 (1.97), 7.526(2.61), 7.532 (7.59), 7.536 (6.59), 7.590 (1.03), 7.604 (1.42), 7.607(1.87), 7.621 (2.19), 7.645 (2.30), 7.648 (2.42), 7.656 (0.71), 7.662(1.26), 7.665 (1.03), 7.736 (2.01), 7.739 (1.84), 7.749 (2.20), 7.752(1.94), 7.764 (0.48), 7.766 (0.43), 7.818 (0.54), 7.821 (0.50), 7.835(0.46), 9.108 (1.57), 9.133 (5.65). 655 LC-MS ¹H-NMR (500 MHz, DMSO-d6)δ [ppm]: (Method 1.311 (7.80), 1.327 (16.00), 1.341 (7.58), L1): 2.033(1.52), 2.041 (1.61), 2.047 (1.74), Rt = 1.18 2.054 (1.78), 2.061(2.13), 2.067 (1.87), min; MS 2.198 (1.93), 2.207 (1.91), 2.215 (1.83),(ESIpos): 3.235 (2.53), 3.250 (6.81), 3.265 (6.83), m/z = 463 3.279(3.01), 4.227 (1.01), 4.244 (3.29), [M + H]⁺ 4.258 (5.03), 4.264 (5.39),4.276 (3.07), 4.290 (0.97), 5.288 (1.40), 5.300 (2.99), 5.315 (2.94),5.327 (1.35), 6.781 (5.15), 6.797 (5.61), 6.909 (2.60), 6.924 (5.33),6.939 (3.03), 7.151 (2.73), 7.165 (4.53), 7.180 (2.23), 7.228 (2.53),7.236 (2.62), 7.345 (4.77), 7.360 (4.45), 7.601 (2.02), 7.607 (2.10),7.614 (2.02), 7.782 (2.66), 7.797 (5.11), 7.813 (4.47), 7.845 (6.38),7.857 (3.89), 8.374 (4.77), 8.389 (4.49), 8.789 (13.74), 9.121 (4.49,9.137 (4.40). 676 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 1.319(6.59), 1.334 (14.59), 1.349 (6.59), L1): 1.869 (13.65), 2.031 (1.41),2.052 (1.88), Rt = 1.27 2.059 (1.41), 2.200 (1.41), 2.292 (16.00), min;MS 2.362 (1.41), 2.636 (1.88), 3.236 (3.29), (ESIpos): 3.251 (3.76),3.375 (0.94), 3.418 (0.94), m/z = 437 4.238 (2.35), 4.253 (3.29), 4.259(3.76), [M + H]⁺ 4.271 (2.35), 5.282 (0.94), 5.295 (1.88), 5.310 (1.88),6.778 (4.24), 6.793 (4.71), 6.901 (1.88), 6.916 (4.24), 6.931 (2.35),6.962 (5.18), 7.099 (2.35), 7.114 (4.24), 7.147 (2.35), 7.157 (5.18),7.171 (3.29), 7.330 (3.29), 7.345 (2.82), 7.590 (4.24), 7.592 (4.24),7.604 (5.18), 7.606 (4.71), 7.712 (4.24), 7.726 (3.76), 7.729 (4.24),7.743 (3.29), 8.252 (3.76), 8.254 (4.24), 8.269 (3.76), 8.689 (13.65),9.070 (2.35), 9.088 (1.88). 684 LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]:(Method −0.120 (0.78), −0.007 (5.46), 0.007 L1): (3.90), 0.117 (0.39),1.520 (12.10), 1.523 Rt = 1.28 (11.71), 1.534 (12.49), 1.538 (11.71),min; MS 1.548 (14.05), 1.563 (13.66), 1.866 (ESIpos): (16.00), 1.884(16.00), 2.036 (1.56), 2.176 m/z = 469 (1.56), 2.281 (16.00), 2.294(16.00), [M + H]⁺ 2.362 (1.95), 2.636 (1.56), 3.363 (1.17), 3.853(1.95), 4.219 (2.34), 4.245 (2.34), 4.252 (2.73), 4.259 (2.34), 4.266(2.34), 5.248 (2.73), 5.264 (2.34), 6.771 (5.46), 6.786 (5.85), 6.892(2.73), 6.906 (5.46), 6.924 (5.46), 6.948 (3.51), 7.131 (3.51), 7.138(3.12), 7.142 (3.90), 7.147 (5.07), 7.169 (2.34), 7.206 (3.90), 7.215(3.90), 7.221 (2.73), 7.230 (2.73), 7.318 (3.90), 7.333 (3.51), 7.642(3.51), 7.660 (5.46), 7.678 (3.51), 8.473 (3.12), 8.484 (3.51), 8.492(3.51), 8.504 (3.12), 8.640 (11.32), 8.643 (10.54), 9.075 (2.73), 9.082(2.73), 9.092 (2.73), 9.098 (2.73). 685 LC-MS ¹H-NMR (500 MHz, DMSO-d6)δ [ppm]: (Method −0.007 (1.56), 0.006 (1.12), 1.861 (5.14), L1): 2.038(0.49), 2.044 (0.51), 2.052 (0.51), Rt = 1.18 2.058 (0.54), 2.066(0.72), 2.072 (0.58), min; MS 2.079 (0.42), 2.185 (0.47), 2.195 (0.63),(ESIpos): 2.205 (0.63), 2.212 (0.58), 2.297 (7.94), m/z = 423 2.778(16.00), 4.237 (0.98), 4.243 (0.79), [M + H]⁺ 4.254 (1.52), 4.261(1.45), 4.268 (0.93), 4.275 (0.98), 5.278 (0.42), 5.290 (0.91), 5.306(0.89), 5.317 (0.40), 6.779 (1.89), 6.781 (1.96), 6.796 (2.10), 6.798(2.06), 6.899 (0.84), 6.915 (1.68), 6.929 (0.96), 6.965 (2.03), 7.101(1.03), 7.116 (1.78), 7.145 (1.00), 7.148 (1.10), 7.157 (2.34), 7.172(1.31), 7.179 (0.84), 7.335 (1.31), 7.350 (1.19), 7.599 (1.92), 7.602(1.92), 7.613 (2.38), 7.616 (2.27), 7.714 (1.96), 7.728 (1.78), 7.731(2.15), 7.745 (1.64), 8.219 (2.08), 8.222 (2.13), 8.236 (1.96), 8.239(1.82), 8.701 (6.47), 9.043 (1.66), 9.060 (1.66). 686 LC-MS ¹H-NMR (600MHz, DMSO-d6) δ [ppm]: (Method 0.005 (1.04), 2.043 (0.47), 2.048 (0.60),L1): 2.053 (0.96), 2.058 (1.04), 2.065 (1.12), Rt = 1.14 2.069 (1.07),2.077 (1.37), 2.081 (1.20), min; MS 2.087 (2.11), 2.092 (0.63), 2.193(0.58), (ESIpos): 2.199 (0.86), 2202 (0.81), 2.207 (1.32), m/z = 4792.213 (0.97), 2.216 (1.31), 2.221 (1.32), [M + H]⁺ 2.230 (0.99), 2.236(0.64), 2.239 (0.62), 2.244 (0.46), 2.793 (0.55), 3.345 (8.00), 4.220(0.71), 4.225 (0.87), 4.234 (0.90), 4.239 (2.32), 4.244 (1.61), 4.253(1.77), 4.258 (1.47), 4.268 (1.42), 4273 (1.80), 4.279 (1.58), 4.285(1.91), 4.292 (0.78), 4.298 (0.84), 4.303 (0.65), 5.037 (16.00), 5.287(0.91), 5.297 (1.95), 5.310 (1.96), 5.320 (0.92), 6.790 (3.66), 6.791(3.76), 6.803 (4.00), 6.804 (3.99), 6.917 (1.85), 6.918 (1.84), 6.929(3.75), 6.931 (3.68), 6.942 (2.14), 6.943 (2.05), 7.159 (1.78), 7.161(1.80), 7.173 (3.01), 7.184 (1.56), 7.187 (1.49), 7.259 (1.51), 7.267(1.49), 7.274 (1.49), 7.376 (3.08), 7.388 (2.95), 7.609 (0.49), 7.614(0.63), 7.619 (0.75), 7.624 (1.18), 7.628 (1.14), 7.633 (1.23), 7.638(1.18), 7.642 (1.18), 7.646 (0.74), 7.651 (0.65), 7.657 (0.56), 7.800(2.66), 7.812 (3.85), 7.814 (3.18), 7.826 (3.61), 7.873 (4.17), 7.875(4.29), 7.885 (3.06), 7.887 (2.94), 8.416 (3.61), 8.418 (3.65), 8.430(3.48), 8.432 (3.27), 8.890 (12.74), 9.184 (3.52), 9.197 (3.43). 687LC-MS ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: (Method 1.306 (6.83), 1.321(15.00), 1.336 (6.50), L1): 2.030 (0.50), 2.043 (1.17), 2.050 (1.17), Rt= 1.24 2.058 (1.17), 2.064 (1.33), 2.072 (6.00), min; MS 2.078 (1.33),2.084 (1.00), 2.091 (0.67), (ESIpos): 2.187 (0.67), 2.194 (1.17), 2.205(1.33), m/z = 445 2.214 (1.33), 2.222 (1.17), 2.234 (0.83), [M + H]⁺2.248 (0.50), 2.363 (0.50), 2.637 (0.50), 3.235 (1.83), 3.250 (5.50),3.265 (5.67), 3.280 (2.50), 3.352 (3.17), 3.358 (2.17), 3.365 (1.17),3.376 (0.83), 3.429 (0.50), 4.236 (0.83), 4.251 (2.67), 4.261 (2.83),4.266 (3.50), 4.270 (3.67), 4.274 (3.67), 4.282 (2.33), 4.297 (0.67),5.298 (1.00), 5.310 (2.17), 5.326 (2.17), 5.337 (1.00), 6.786 (4.17),6.788 (4.33), 6.802 (4.67), 6.804 (4.50), 6.916 (2.17), 6.918 (2.17),6.931 (4.33), 6.933 (4.17), 6.945 (2.67), 6.948 (2.50), 7.153 (2.17),7.156 (2.17), 7.170 (3.50), 7.184 (1.83), 7.187 (1.67), 7.257 (0.83),7.261 (1.67), 7.266 (1.33), 7.276 (1.67), 7.280 (3.50), 7.285 (2.33),7.294 (1.00), 7.299 (1.67), 7.304 (1.17), 7.333 (4.67), 7.337 (5.17),7.350 (8.83), 7.364 (3.83), 7.757 (3.17), 7.771 (4.50), 7.774 (3.83),7.788 (4.17), 7.868 (5.17), 7.871 (5.17), 7.882 (4.00), 7.885 (3.67),8.316 (4.00), 8.318 (4.00), 8.333 (3.83), 8.335 (3.50), 8.828 (16.00),9.103 (3.67), 9.120 (3.67). 688 LC-MS ¹H-NMR (600 MHz, DMSO-d6): d(Method [ppm] = 9.15 (d, 1H), 8.78 (s, 1H), 8.37 L1): (dd, 1H), 7.83 (d,1H), 7.80 (d, 1H), Rt = 1.21 7.47-7.40 (m, 1H), 7.37-7.31 (m, 2H), min;MS 7.17 (t, 1H), 6.93 (t, 1H), 6.79 (d, 1H), (ESIpos): 5.33-5.29 (m,1H), 4.30-4.22 (m, 2H), m/z = 463 3.33-3.20 (m, 2H), 2.24-2.17 (m, 1H),[M + H]⁺ 2.09-2.01 (m, 1H), 1.33 (t, 3H) 695 LC-MS ¹H-NMR (600 MHz,DMSO-d6) δ [ppm]: (Method 2.063 (0.84), 2.069 (0.94), 2.074 (0.95), L1):2.081 (1.08), 2.086 (1.02), 2.209 (1.01), Rt = 1.17 2.217 (1.02), 2.223(0.98), 2.231 (0.76), min; MS 2.790 (16.00), 4.237 (0.59) 4.250 (1.61),(ESIpos): 4.255 (1.39), 4.269 (2.17), 4.275 (1.71), m/z = 431 4.280(1.46), 4.286 (1.51), 4.299 (0.61), [M + H]⁺ 5.297 (0.70), 5.307 (1.52),5.319 (1.53), 5.329 (0.70), 5.762 (2.23), 6.793 (2.52), 6.807 (2.70),6.919 (1.29), 6.932 (2.60), 6.944 (1.48), 7.162 (1.32), 7.174 (2.26),7.187 (1.14), 7.280 (0.92), 7.295 (1.78), 7.311 (0.98), 7.349 (3.64),7.358 (5.29), 7.369 (3.11), 7.762 (1.45), 7.774 (2.50), 7.788 (1.76),7.885 (2.83), 7.897 (2.35), 8.285 (2.53), 8.299 (2.38), 8.841 (5.87),9.107 (2.25), 9.120 (2.21).

Table 3a-3e: Intermediates

TABLE 3a 1Q-OEt

Number R3 R4 R5 R6 Q 1Q-1 H H H H 3,5-dichlorophenyl 1Q-2 H H H H2,3,5-trichlorophenyl 1Q-3 H H H H 2,3-dichlorophenyl 1Q-4 H H H H3,5-difluorophenyl 1Q-5 H H H H 2,3,5-trifluorophenyl 1Q-6 H H H H2,3-difluorophenyl 1Q-7 H F H H 3,5-dichlorophenyl 1Q-8 H F H H2,3,5-trichlorophenyl 1Q-9 H F H H 2,3-dichlorophenyl 1Q-10 H F H H3,5-difluorophenyl 1Q-11 H F H H 2,3,5-trifluorophenyl 1Q-12 H F H H2,3-difluorophenyl 1Q-13 H H H H 3,5-dimethylphenyl

TABLE 3b 1U-OEt

Number R2 R3 R4 R5 R6 Q 1U-1 dimethylamino H H H H 3,5-dichlorophenyl1U-2 dimethylamino H H H H 2,3,5-trichlorophenyl 1U-3 dimethylamino H HH H 2,3-dichlorophenyl 1U-4 dimethylamino H H H H 3,5-difluorophenyl1U-5 dimethylamino H H H H 2,3,5-trifluorophenyl 1U-6 dimethylamino H HH H 2,3-difluorophenyl 1U-7 dimethylamino H F H H 3,5-dichlorophenyl1U-8 dimethylamino H F H H 2,3,5-trichlorophenyl 1U-9 dimethylamino H FH H 2,3-dichlorophenyl 1U-10 dimethylamino H F H H 3,5-difluorophenyl1U-11 dimethylamino H F H H 2,3,5-trifluorophenyl 1U-12 dimethylamino HF H H 2,3-difluorophenyl 1U-13 morpholin-4-yl H H H H 3,5-dichlorophenyl1U-14 morpholin-4-yl H H H H 2,3,5-trichlorophenyl 1U-15 morpholin-4-ylH H H H 2,3-dichlorophenyl 1U-16 morpholin-4-yl H H H H3,5-difluorophenyl 1U-17 morpholin-4-yl H H H H 2,3,5-trifluorophenyl1U-18 morpholin-4-yl H H H H 2,3-difluorophenyl 1U-19 morpholin-4-yl H FH H 3,5-dichlorophenyl 1U-20 morpholin-4-yl H F H H2,3,5-trichlorophenyl 1U-21 morpholin-4-yl H F H H 2,3-dichlorophenyl1U-22 morpholin-4-yl H F H H 3,5-difluorophenyl 1U-23 morpholin-4-yl H FH H 2,3,5-trifluorophenyl 1U-24 morpholin-4-yl H F H H2,3-difluorophenyl

TABLE 3c 1R

Number R3 R4 R5 R6 Q 1R-1 H H H H 3,5-dichlorophenyl 1R-2 H H H H2,3,5-trichlorophenyl 1R-3 H H H H 2,3-dichlorophenyl 1R-4 H H H H3,5-difluorophenyl 1R-5 H H H H 2,3,5-trifluorophenyl 1R-6 H H H H2,3-difluorophenyl 1R-7 H F H H 3,5-dichlorophenyl 1R-8 H F H H2,3,5-trichlorophenyl 1R-9 H F H H 2,3-dichlorophenyl 1R-10 H F H H3,5-difluorophenyl 1R-11 H F H H 2,3,5-trifluorophenyl 1R-12 H F H H2,3-difluorophenyl 1R-13 H H H H 3,5-dimethylphenyl

TABLE 3d 1W

Number R2 R3 R4 R5 R6 Q 1W-1 dimethylamino H H H H 3,5-dichlorophenyl1W-2 dimethylamino H H H H 2,3,5-trichlorophenyl 1W-3 dimethylamino H HH H 2,3-dichlorophenyl 1W-4 dimethylamino H H H H 3,5-difluorophenyl1W-5 dimethylamino H H H H 2,3,5-trifluorophenyl 1W-6 dimethylamino H HH H 2,3-difluorophenyl 1W-7 dimethylamino H F H H 3,5-dichlorophenyl1W-8 dimethylamino H F H H 2,3,5-trichlorophenyl 1W-9 dimethylamino H FH H 2,3-dichlorophenyl 1W-10 dimethylamino H F H H 3,5-difluorophenyl1W-11 dimethylamino H F H H 2,3,5-trifluorophenyl 1W-12 dimethylamino HF H H 2,3-difluorophenyl 1W-13 morpholin-4-yl H H H H 3,5-dichlorophenyl1W-14 morpholin-4-yl H H H H 2,3,5-trichlorophenyl 1W-15 morpholin-4-ylH H H H 2,3-dichlorophenyl 1W-16 morpholin-4-yl H H H H3,5-difluorophenyl 1W-17 morpholin-4-yl H H H H 2,3,5-trifluorophenyl1W-18 morpholin-4-yl H H H H 2,3-difluorophenyl 1W-19 morpholin-4-yl H FH H 3,5-dichlorophenyl 1W-20 morpholin-4-yl H F H H2,3,5-trichlorophenyl 1W-21 morpholin-4-yl H F H H 2,3-dichlorophenyl1W-22 morpholin-4-yl H F H H 3,5-difluorophenyl 1W-23 morpholin-4-yl H FH H 2,3,5-trifluorophenyl 1W-24 morpholin-4-yl H F H H2,3-difluorophenyl

TABLE 3e 1T-Br

Number R1 R2 R3 R4 R5 R6 A 1T-1 H dimethylamino H H H H(4S)-3,4-dihydro-2H- chromen-4-yl 1T-2 H dimethylamino H H H H(1S)-2,3-dihydro-1H- inden-1-yl 1T-3 H dimethylamino H F H H(4S)-3,4-dihydro-2H- chromen-4-yl 1T-4 H dimethylamino H F H H(1S)-2,3-dihydro-1H- inden-1-yl 1T-5 H morpholin-4-yl H H H H(4S)-3,4-dihydro-2H- chromen-4-yl 1T-6 H morpholin-4-yl H H H H(1S)-2,3-dihydro-1H- inden-1-yl 1T-7 H morpholin-4-yl H F H H(4S)-3,4-dihydro-2H- chromen-4-yl 1T-8 H morpholin-4-yl H F H H(1S)-2,3-dihydro-1H- inden-1-yl

TABLE 4 LC-MS and NMR or NMR Peaklist of Intermediates logP LC-MSExample No (Method L0) ^([a]) (Method L2-L5) NMR or NMR Peaklist 1-Q35.19 ¹H-NM R (400.0 MHz, d₆-DMSO): δ = 9.100 (11.2); 8.521 (2.9); 8.516(3.1); 8.501 (3.1); 8.496 (3.3); 7.983 (1.5); 7.965 (4.5); 7.945 (9.0);7.941 (6.3); 7.928 (1.8); 7.756 (2.9); 7.752 (3.4); 7.736 (3.6); 7.732(3.8); 7.504 (2.2); 7.485 (5.2); 7.465 (3.5); 7.434 (4.1); 7.431 (4.7);7.415 (2.5); 7.412 (2.4); 4.454 (2.4); 4.436 (7.3); 4.418 (7.3); 4.400(2.5); 3.321 (80.5); 2.891 (0.5); 2.731 (0.5); 2.672 (1.1); 2.502(195.0); 2.329 (1.1); 2.075 (1.2); 1.387 (7.9); 1.369 (16.0); 1.351(7.7); 0.146 (0.4); 0.000 (90.1); −0.150 (0.5) 1Q-13 LC-MS (Method L1):Rt = 1.43 1H-NMR (400MHz, DMSO-d6): δ [ppm] = 9.13 (s, 1H), 8.42 (dd,1H), 7.87-7.96 (m, 2H), 7.20 (s, 2H), 7.07 (s, 1H), 4.44 (q, min; MS(ESIpos): m/z = 340 2H), 2.35 (s, 6H), 1.38 (t, 3H). [M +H]⁺ 1U-5 2.401H-NMR (400MHz, DMSO-d6): δ [ppm] = 8.73 (s, 1H), 8.35 (d, 1H), 7.83 (d,1H), 7.72-7.69 (t, 1H), 7.61-7.58 (m, 1H), 7.24-7.22 (m, 1H), 4.41-4.35(q, 2H), 3.09 (s, 6H), 1.36 (t, 3H). 1U-8 4.57 ¹H-NMR (400.0 MHz,d₆-DMSO): δ = 8.857 (1.9); 8.703 (3.6); 8.425 (0.7); 8.409 (0.8); 8.401(0.8); 8.386 (0.7); 8.305 (0.4); 8.290 (0.5); 8.281 (0.5); 8.266 (0.5);7.967 (2.0); 7.961 (2.1); 7.687 (0.8); 7.664 (1.2); 7.647 (0.5); 7.641(0.8); 7.626 (0.5); 7.623 (0.5); 7.603 (0.4); 7.586 (2.0); 7.580 (2.0);5.758 (5.2); 4.420 (0.4); 4.403 (1.3); 4.391 (0.8); 4.385 (1.4); 4.374(2.3); 4.367 (0.6); 4.356 (2.3); 4.338 (0.7); 3.326 (10.9); 3.094(16.0); 3.071 (9.4); 2.514 (7.9); 2.509 (15.9); 2.505 (21.1); 2.500(15.4); 2.496 (7.6); 1.382 (1.4); 1.364 (3.0); 1.357 (2.6); 1.346 (1.6);1.339 (5.3); 1.321 (2.4); 1.299 (0.5); 1.269 (0.5); 0.008 (0.8); 0.000(20.5); −0.008 (0.9) 1U-11 2.40 ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.730(3.6); 8.348 (1.0); 8.345 (0.9); 8.327 (1.1); 7.828 (0.9); 7.813 (1.3);7.725 (1.0); 7.707 (1.0); 7.704 (1.0); 7.686 (0.7); 7.607 (0.4); 7.601(0.4); 7.594 (0.4); 7.586 (0.4); 7.581 (0.4); 7.243 (0.5); 7.233 (0.4);7.221 (0.5); 4.407 (0.8); 4.390 (2.4); 4.372 (2.4); 4.354 (0.8); 3.327(5.3); 3.089 (16.0); 2.509 (10.6); 2.505 (13.3); 2.501 (9.7); 1.397(10.3); 1.372 (2.5); 1.355 (5.2); 1.337 (2.4); 0.008 (0.5); 0.000(10.8); −0.009 (0.5) 1U-13 5.19 LC-MS (Method 1): Rt = 2.36 ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 8.829 (5.1); 8.335 (1.1); 8.332 (1.2); 8.314(1.2); 8.311 (1.2); 7.900 (1.1); 7.897 (1.2); 7.882 (1.5); min; m/z =431/433 (M + H)⁺ 7.879 (1.4); 7.759 (1.2); 7.740 (1.3); 7.737 (1.4);7.719 (0.9); 7.646 (16.0); 4.441 (0.9); 4.423 (3.1); 4.405 (3.1); 4.388(1.0); 3.896 (2.6); 3.885 (3.5); 3.874 (2.7); 3.320 (6.3); 3.273 (2.7);3.262 (3.4); 3.251 (2.4); 2.525 (0.6); 2.511 (14.8); 2.507 (30.3); 2.503(39.9); 2.498 (28.5); 2.494 (13.8); 1.397 (6.5); 1.376 (7.1); 1.359(3.3); 0.000 (3.3) 1U-15 3.90 LC-MS (Method 1): R_(t) = 2.17 ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 8.726 (8.4); 8.345 (1.6); 8.337 (1.6); 8.327(1.7); 8.320 (1.8); 7.768 (0.8); 7.751 (3.0); 7.740 (3.4); min; m/z =431/433 (M + H)⁺ 7.733 (6.7); 7.723 (1.0); 7.713 (2.2); 7.709 (2.3);7.693 (2.5); 7.689 (2.5); 7.468 (1.8); 7.448 (3.6); 7.429 (2.2); 7.369(2.7); 7.366 (2.8); 7.350 (1.9); 7.347 (1.7); 4.427 (1.5); 4.409 (4.8);4.391 (4.9); 4.373 (1.6); 3.899 (4.4); 3.887 (8.0); 3.876 (4.6); 3.321(37.8); 3.293 (2.5); 3.282 (5.5); 3.270 (5.3); 3.259 (2.2); 3.239 (0.6);2.671 (0.4); 2.506 (61.9); 2.502 (81.2); 2.498 (60.0); 2.329 (0.5);1.397 (16.0); 1.380 (5.5); 1.362 (11.1); 1.344 (5.2); 0.008 (2.2); 0.000(45.4) 1R-1 LC-MS (Method L1): R_(t) = 1.16 1H-NMR (400 MHz, DMSO-d6) δ[ppm]: −0.008 (1.29), 0.008 (1.20), 1.760 (0.44), 2.329 (0.64), 2.367(0.44), 2.524 (2.38), min; MS (ESIpos): m/z = 352 2.671 (0.63), 2.711(0.43), 3.601 (0.50), 7.654 (1.72), 7.660 (4.30), 7.664 (6.77), 7.669(16.00), 7.673 (7.64), 7.804 (1.91), [M + H]⁺ 7.823 (3.49), 7.843(3.22), 7.887 (3.53), 7.890 (3.71), 7.904 (2.79), 8.354 (3.04), 8.357(3.11), 8.375 (2.85), 8.378 (2.73), 8.907 (6.32). 1R-3 LC-MS (MethodL1): R_(t) = 1.05 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.175 (0.47), 1.356(0.45), 1.989 (0.90), 2.074 (8.95), 2.329 (0.81), 2.369 (0.60), min; MS(ESIpos): m/z = 352 2.671 (0.95), 2.711 (0.65), 2.865 (0.47), 3.092(0.78), 7.362 (0.70), 7.381 (1.05), 7.409 (6.34), 7.427 (11.32), 7.462(7.73), [M + H]⁺ 7.481 (11.58), 7.500 (5.55), 7.530 (1.06), 7.550(0.60), 7.585 (0.87), 7.693 (1.21), 7.728 (9.06), 7.747 (7.85), 7.895(5.45), 7.911 (13.10), 7.923 (10.39), 7.943 (10.33), 7.961 (4.26), 7.992(0.98), 8.009 (0.69), 8.448 (0.92), 8.485 (8.46), 8.505 (8.03), 9.072(16.00), 9.141 (1.24), 14.022 (0.91). 1R-13 LC-MS (Method L1): R_(t) =1.15 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.346 (16.00), 7.062 (1.52),7.189 (3.52), 7.884 (1.52), 7.895 (1.68), 7.902 (3.49), min; MS(ESIpos): m/z = 312 8.396 (0.99), 8.403 (0.92), 8.414 (0.88), 8.421(0.87), 9.116 (2.83). [M + H]⁺ 1W-8 2.17 ¹H-NMR (400.0 MHz, d₆-DMSO): δ= 8.717 (3.1); 8.422 (0.7); 8.406 (0.8); 8.399 (0.9); 8.383 (0.8); 7.965(2.0); 7.960 (2.1); 7.823 (0.5); 7.815 (0.5); 7.809 (0.5); 7.796 (0.6);7.783 (0.6); 7.675 (0.9); 7.652 (1.4); 7.630 (0.9); 7.586 (2.0); 7.580(2.0); 7.502 (0.4); 7.478 (0.7); 7.466 (1.1); 7.385 (0.6); 7.344 (0.6);6.579 (0.3); 3.328 (75.7); 3.106 (16.0); 3.077 (0.5); 2.671 (0.7); 2.549(1.8); 2.503 (106.1); 2.339 (0.8); 2.329 (0.8); 2.324 (0.7); 1.271(0.7); 1.170 (2.7); 0.146 (0.4); 0.000 (76.2); −0.150 (0.4) 1W-15 1.86LC-MS (Method 1): Rt = 1.78 ¹H-NMR (400.0 MHz, d₆-DMSO): δ = 8.449(15.5); 8.278 (3.9); 8.275 (4.0); 8.257 (4.4); 8.254 (4.3); 7.688 (4.2);7.684 (4.3); 7.668 (5.2); min; m/z = 403/405 (M + H)⁺ 7.664 (5.0); 7.603(3.0); 7.586 (4.8); 7.565 (4.2); 7.502 (5.2); 7.499 (5.4); 7.484 (3.9);7.481 (3.6); 7.447 (3.6); 7.428 (7.2); 7.408 (4.5); [mass of free base]7.343 (5.4); 7.339 (5.5); 7.324 (4.0); 7.320 (3.6); 3.823 (9.2); 3.812(16.0); 3.801 (9.9); 3.601 (0.4); 3.353 (665.1); 3.325 (9.0); 3.314(7.9); 2.672 (0.7); 2.508 (106.3); 2.503 (137.7); 2.499 (101.0); 2.330(0.8); 1.759 (0.5); 0.000 (19.5) 1-T1 LC-MS (Method L1): R_(t) = 0.731H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.050 (16.00), 4.241 (0.59), 4.249(0.48), 4.262 (0.64), 4.268 (0.76), 4.276 (0.62), min; MS (ESIpos): m/z= 426 4.283 (0.49), 4.292 (0.50), 5.245 (0.56), 5.264 (0.55), 6.794(0.98), 6.814 (1.10), 6.919 (0.49), 6.938 (1.05), 6.956 (0.61), [M + H]⁺7.163 (0.52), 7.181 (0.86), 7.198 (0.40), 7.362 (0.91), 7.381 (0.84),7.441 (0.75), 7.461 (1.18), 7.481 (0.82), 8.082 (1.07), 8.099 (1.02),8.159 (1.09), 8.180 (1.03), 8.680 (3.34), 9.095 (0.82), 9.115 (0.80).1-T5 LC-MS (Method L1): R_(t) = 0.92 1H-NMR (400 MHz, DMSO-d6) δ [ppm]:−0.149 (0.41), −0.008 (4.42), 0.008 (3.18), 2.041 (0.54), 2.048 (0.76),2.056 (1.13), min; MS (ESIneg): m/z = 466 2.063 (1.19), 2.076 (1.30),2.091 (1.80), 2.098 (1.57), 2.106 (1.11), 2.197 (0.74), 2.206 (1.17),2.218 (1.70), 2.231 (1.59), [M − H]⁻ 2.240 (1.58), 2.253 (1.13), 2.262(0.74), 2.274 (0.52), 2.327 (0.60), 2.366 (0.49), 2.523 (2.30), 2.669(0.66), 2.710 (0.48), 3.217 (0.69), 3.228 (1.18), 3.248 (4.71), 3.258(11.00), 3.269 (11.28), 3.279 (5.00), 3.842 (8.92), 3.853 (14.13), 3.864(8.07), 4.214 (0.80), 4.221 (1.01), 4.242 (2.68), 4.249 (2.03), 4.263(2.41), 4.271 (2.08), 4.276 (2.00), 4.286 (2.44), 4.293 (2.07), 4.302(2.18), 4.314 (0.86), 4.321 (0.96), 4.329 (0.65), 5.245 (1.10), 5.259(2.45), 5.279 (2.44), 5.292 (1.06), 6.797 (4.29), 6.815 (4.84), 6.927(2.26), 6.929 (2.16), 6.946 (4.75), 6.964 (2.87), 7.164 (2.33), 7.167(2.40), 7.185 (3.85), 7.202 (1.91), 7.206 (1.79), 7.385 (4.05), 7.403(3.77), 7.499 (3.74), 7.518 (5.40), 7.538 (4.06), 8.123 (4.80), 8.125(5.04), 8.142 (4.71), 8.144 (4.51), 8.197 (4.92), 8.199 (4.64), 8.218(4.71), 8.753 (16.00), 9.177 (3.99), 9.197 (3.89). 1-T7 2.69 ¹H-NMR(400.0 MHz, d₆-DMSO): δ = 9.220 (2.1); 9.200 (2.1); 8.789 (9.2); 8.283(1.8); 8.268 (1.9); 8.260 (2.0); 8.244 (1.9); 7.671 (2.0); 7.650 (2.6);7.627 (1.8); 7.402 (2.0); 7.385 (2.2); 7.203 (1.1); 7.186 (2.2); 7.169(1.3); 7.165 (1.3); 6.964 (1.6); 6.945 (2.6); 6.929 (1.3); 6.926 (1.2);6.819 (2.9); 6.798 (2.7); 5.286 (0.6); 5.272 (1.3); 5.252 (1.3); 5.238(0.6); 4.329 (0.4); 4.320 (0.5); 4.312 (0.5); 4.301 (1.1); 4.292 (1.1);4.284 (1.3); 4.276 (1.0); 4.267 (1.1); 4.260 (1.3); 4.246 (1.1); 4.238(1.4); 4.218 (0.5); 4.211 (0.5); 3.865 (4.4); 3.854 (7.4); 3.843 (4.7);3.726 (3.9); 3.715 (4.8); 3.703 (4.1); 3.568 (16.0); 3.487 (0.4); 3.332(12.7); 3.280 (4.6); 3.270 (7.3); 3.259 (6.7); 3.229 (1.2); 3.023 (3.6);3.011 (4.6); 2.999 (3.4); 2.675 (0.7); 2.671 (0.9); 2.666 (0.7); 2.510(61.4); 2.506 (124.6); 2.502 (165.2); 2.497 (119.8); 2.329 (1.0); 2.272(0.4); 2.261 (0.5); 2.250 (0.6); 2.237 (0.9); 2.228 (0.9); 2.215 (1.0);2.202 (0.7); 2.193 (0.4); 2.103 (0.6); 2.095 (0.8); 2.088 (1.0); 2.071(0.8); 2.060 (0.7); 2.053 (0.6); 1.470 (0.4); 0.936 (0.4); 0.008 (1.0);0.000 (24.6); −0.008 (1.1)

EXPERIMENTAL SECTION—BIOLOGICAL ASSAYS

Examples were tested in selected biological assays one or more times.When tested more than once, data are reported as either average valuesor as median values, wherein

-   -   the average value, also referred to as the arithmetic mean        value, represents the sum of the values obtained divided by the        number of times tested, and    -   the median value represents the middle number of the group of        values when ranked in ascending or descending order. If the        number of values in the data set is odd, the median is the        middle value. If the number of values in the data set is even,        the median is the arithmetic mean of the two middle values.

Examples were synthesized one or more times. When synthesized more thanonce, data from biological assays represent average values or medianvalues calculated utilizing data sets obtained from testing of one ormore synthetic batch.

The in vitro activity of the compounds of the present invention can bedemonstrated in the following assays:

In Vitro Assay 1: C. elegans Slo-1a—Action at a Recombinant C. elegansCell Line

Generation of a Stable C. elegans CHO Cell Line

A CHO cell line was obtained from ATCC, code ATCC CRL-9096. Fortransfection with plasmid DNA to express C. elegans Slo-1a (accessionnumber AAL28102) CHO cells were passaged to 40% confluence before addingthe transfection solution to the cell culture. The transfection solutionincluded 300 μL OptiMEM (Life Technologies, Nr.: 31985), 2 μL (=6 μg) ofplasmid DNA containing the C. elegans Slo 1a gene and 9 μL FugeneHD(Promega, Nr.: E2311), and was added to the cells prior to incubationfor 48 hours at 37° C., 5% CO₂. The transfection medium was exchangedfor the selection medium which contains additional G418 (2 mg/ml,Invitrogen, Nr.: 10131) and the cells were seeded into 384 well plates(300 cells/well). After a few weeks, the remaining surviving cells weretested with a voltage sensitive dye (Membrane Potential Assay Kit,Molecular Devices Nr.: R8034) for K+ channel expression. Positive cellclones were purified by the limited dilution technique. For this theclone with the highest and most robust signal in the voltage sensitivedye assay was further subcloned (incubated) in 384 well plates (0.7cells/well) in order to obtain clonal purity. This generated a finalstable CHO cell line expressing the C. elegans Slo-1a.

Cell Culture Conditions

Cells were cultured at 37° C. and 5% CO₂ in MEMalpha with Gutamax I(Invitrogen, Nr.: 32571), supplemented with 10% (v/v) heat inactivatedfetal bovine serum (Invitrogen, Nr.: 10500), G418 (1 mg/ml, Invitrogen,Nr.: 10131). Cells were detached using Accutase (Sigma, Nr.: A6964).

Membrane Potential Measurements

Laboratory compound testing was performed on 384-well microtiter plates(MTPs, Greiner, Nr.: 781092). 8000 cells/well were plated onto 384-wellMTPs and cultured for 20 to 24 hours at 37° C. and 5% CO₂. After removalof the cell culture medium, the cells were washed once with tyrode (150mM NaCl, 0.3 mM KCl, 2 mM CaCl₂, 1 mM MgCl₂, 0.8 mM NaH₂PO₄, 5 mMGlucose, 28 mM Hepes, pH 7.4) and then loaded with the voltage sensitivedye of the Membrane Potential Assay Kit diluted in tyrode for 1 h atroom temperature.

After starting the measurement of fluorescence using a FLIPR Tetra(Molecular Devices, Exc. 510-545 nm, Emm. 565-625 nm), test compoundswere added followed by the addition of KCl tyrode (final assayconcentration: 70 mM KCl, 2 mM CaCl₂, 1 mM MgCl₂, 0.8 mM NaH₂PO₄, 5 mMGlucose, 28 mM Hepes, pH 7.4, including the voltage sensitive dye). Themeasurement was completed after 7 minutes.

Statistics

The data were evaluated by using the ActivityBase XLfit software (IDBS)for curve fitting and calculation of the half-maximal effectiveconcentration (EC₅₀) and are reported as negative decadic logarithm(pE₅₀).

For the following examples, pE₅₀>5.3-6.5 has been found for: 27, 28, 85,87, 88, 109, 131, 182, 183, 243, 345, 361, 363, 402, 424, 440, 510, 511,521, 534, 547, 555, 580, 592, 599, 656.

For the following examples, pE₅₀>6.5-7.5 has been found for: 1, 62, 68,69, 71, 95, 114, 120, 122, 125, 129, 136, 148, 185, 216, 230, 241, 242,246, 264, 276, 289, 299, 324, 346, 354, 372, 379, 389, 390, 399, 401,424, 432, 439, 456, 459, 474, 512, 513, 514, 519, 546, 560, 568, 578,581, 584, 625, 632, 634, 654, 665.

For the following examples, pE₅₀>7.5-8.5 has been found for: 2, 3, 4, 5,6, 23, 55, 58, 63, 64, 65, 66, 73, 74, 90, 93, 98, 102, 110, 117, 119,124, 127, 128, 144, 145, 147, 150, 152, 154, 158, 159, 163, 173, 180,188, 195, 196, 203, 204, 212, 213, 218, 219, 224, 229, 231, 232, 236,245, 252, 253, 255, 257, 258, 259, 263, 266, 268, 269, 270, 273, 280,284, 287, 288, 291, 295, 297, 301, 304, 308, 311, 312, 317, 319, 320,321, 323, 325, 342, 343, 344, 348, 360, 370, 375, 378, 380, 381, 383,384, 385, 386, 391, 392, 393, 394, 397, 403, 405, 412, 429, 433, 434,443, 447, 454, 457, 458, 460, 461, 463, 464, 466, 471, 472, 473, 475,476, 480, 481, 482, 483, 484, 486, 493, 494, 495, 499, 500, 501, 502,503, 507, 508, 509, 515, 517, 518, 522, 523, 524, 525, 526, 527, 528,529, 530, 531, 532, 533, 535, 536, 537, 538, 541, 545, 550, 551, 559,561, 562, 563, 566, 567, 569, 570, 571, 572, 573, 574, 575, 577, 579,585, 590, 593, 595, 597, 602, 615, 619, 620, 621, 622, 623, 626, 630,633, 635, 640, 643, 661.

For the following examples, pE₅₀>8.5 has been found for: 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 24, 25, 26, 29, 30, 31,32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 56, 57, 60, 61, 70, 72, 75, 76, 77, 80, 81, 82, 83, 89,100, 101, 108, 112, 115, 121, 130, 132, 133, 134, 135, 137, 138, 139,140, 141, 142, 143, 146, 151, 153, 155, 156, 157, 160, 161, 162, 164,165, 166, 167, 168, 169, 170, 171, 172, 174, 175, 176, 177, 178, 179,181, 184, 186, 187, 189, 190, 191, 192, 193, 194, 197, 200, 201, 205,206, 207, 208, 209, 210, 211, 214, 215, 217, 220, 221, 222, 223, 225,226, 227, 228, 233, 234, 235, 237, 238, 239, 240, 244, 247, 248, 249,250, 251, 254, 256, 260, 261, 262, 265, 267, 271, 272, 274, 275, 277,278, 279, 281, 282, 283, 290, 292, 293, 294, 296, 298, 300, 302, 305,307, 309, 310, 313, 314, 315, 316, 318, 322, 326, 327, 328, 329, 330,331, 332, 333, 334, 335, 338, 339, 340, 341, 349, 350, 351, 352, 353,355, 356, 357, 358, 359, 362, 364, 365, 366, 367, 368, 369, 371, 373,374, 376, 377, 382, 387, 388, 395, 396, 398, 400, 404, 406, 407, 408,409, 410, 411, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423,425, 426, 427, 428, 429, 430, 431, 435, 436, 437, 438, 441, 442, 444,445, 446, 448, 449, 450, 451, 452, 453, 455, 462, 465, 467, 468, 469,470, 477, 478, 479, 485, 487, 488, 489, 490, 491, 492, 496, 497, 498,504, 505, 506, 516, 517, 520, 539, 540, 542, 543, 544, 548, 549, 552,553, 554, 556, 557, 558, 564, 565, 576, 582, 583, 586, 587, 588, 589,591, 594, 596, 598, 600, 601, 603, 604, 605, 606, 607, 608, 609, 610,611, 612, 613, 614, 616, 617, 618, 624, 627, 628, 629, 631, 636, 637,638, 639, 641, 642, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653,655, 657, 658, 659, 660, 662, 663, 664, 666.

In vitro assay 2: Nippostrongylus brasiliensis (NIPOBR)

Adult Nippostrongylus brasiliensis were washed with saline buffercontaining 100 U/ml penicillin, 0.1 mg/ml streptomycin and 2.5 μg/mlamphotericin B. Test compounds were dissolved in DMSO and worms wereincubated in medium in a final concentration of 10 μg/ml (10 ppm)respectively 1 μg/ml (1 ppm). An aliquot of the medium was used todetermine the acetylcholine esterase activity in comparison to anegative control. The principle of measuring acetylcholine esterase asreadout for anthelmintic activity was described in Rapson et al (1986)and Rapson et al (1987).

For the following examples, activity (reduction of AChE compared tonegative control) was higher than 80% at 10 μg/ml: 8, 9, 11, 12, 13, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 31, 32, 33, 34, 35, 36,37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 57,58, 59, 60, 61, 62, 64, 65, 66, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 81, 82, 83, 87, 89, 95, 100, 101, 104, 108, 112, 115, 116, 119, 122,123, 127, 128, 130, 132, 133, 134, 135, 136, 137, 138, 139, 141, 142,143, 144, 146, 147, 148, 333, 334, 336, 338, 339, 340, 341, 349, 362,363, 364, 373, 609, 610, 611, 612, 613, 614, 615, 617, 618, 619, 620,623, 630.

For the following examples, activity (reduction of AChE compared tonegative control) was higher than 80% at 1 μg/ml: 8, 9, 12, 13, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 31, 32, 33, 34, 35, 36, 37,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 57, 58,60, 61, 65, 67, 69, 70, 73, 74, 75, 76, 77, 80, 81, 82, 83, 84, 89, 92,93, 95, 100, 101, 108, 112, 114, 115, 116, 117, 118, 119, 122, 124, 125,126, 127, 128, 129, 130, 132, 133, 134, 135, 136, 137, 138, 139, 142,143, 144, 146, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 160,161, 162, 163, 165, 166, 167, 168, 169, 170, 171, 172, 176, 178, 181,182, 185, 186, 187, 189, 190, 191, 192, 193, 194, 195, 197, 198, 200,201, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 214, 215, 217,218, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 231, 232, 233,234, 235, 236, 237, 238, 239, 240, 247, 249, 250, 251, 254, 256, 257,260, 261, 262, 263, 265, 266, 268, 271, 272, 273, 274, 275, 276, 277,279, 280, 281, 282, 283, 284, 285, 287, 288, 289, 290, 291, 292, 293,294, 301, 302, 307, 308, 309, 310, 311, 313, 314, 315, 318, 319, 321,322, 326, 327, 328, 329, 330, 331, 332, 333, 334, 336, 338, 339, 340,341, 342, 347, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 362,364, 365, 367, 369, 370, 373, 374, 375, 377, 382, 384, 385, 386, 388,392, 394, 395, 396, 397, 400, 403, 404, 406, 407, 408, 409, 410, 411,413, 414, 415, 417, 418, 419, 420, 421, 422, 424, 425, 426, 427, 428,429, 430, 431, 432, 433, 434, 435, 436, 437, 441, 443, 444, 445, 446,447, 448, 449, 450, 451, 452, 453, 454, 455, 458, 460, 461, 462, 463,464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 476, 477, 478, 479,482, 485, 486, 487, 488, 490, 491, 492, 495, 496, 497, 498, 499, 500,501, 504, 505, 506, 507, 508, 509, 516, 517, 520, 527, 528, 529, 530,531, 532, 533, 535, 536, 537, 538, 540, 541, 542, 543, 544, 545, 548,549, 550, 551, 552, 553, 554, 556, 557, 558, 561, 562, 563, 564, 565,566, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 581, 582,583, 585, 586, 587, 588, 590, 594, 596, 597, 598, 601, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 617, 618, 619,620, 623, 624, 626, 627, 628, 629, 631, 632, 633, 634, 635, 636, 637,638, 639, 640, 641, 642, 645, 646, 647, 648, 649, 650, 651, 652, 653,655, 657, 658, 660.

In Vitro Assay 3: Dirofilaria immitis Microfilariae (DIROIM L1)

≥250 Dirofilaria immitis microfilariae, which were freshly purified fromblood, were added to wells of a microtitre plate containing a nutrientmedium and the test compound in DMSO. Compounds were tested inconcentration-response assay in duplicate. Larvae exposed to DMSO and notest compounds were used as negative controls. Larvae were evaluatedafter 72 h of incubation with the compound. Efficacy was determined asthe reduction of motility in comparison to the negative control. Basedon the evaluation of a wide concentration range, concentration-responsecurves as well as EC₅₀-values were calculated.

For the following examples, the EC₅₀ was <0.1 ppm: 1, 4, 5, 6, 7, 8, 9,10, 12, 13, 15, 16, 17, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35,36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 50, 51, 52, 53, 54, 56,57, 58, 60, 61, 64, 65, 69, 73, 74, 76, 77, 80, 81, 82, 83, 84, 89, 101,103, 108, 111, 112, 115, 117, 119, 124, 125, 127, 128, 129, 130, 132,133, 134, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 150, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165,166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,180, 181, 185, 186, 187, 188, 189, 190, 191, 192, 194, 196, 197, 200,201, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 214, 215, 217,218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 231, 232,233, 234, 235, 236, 237, 238, 239, 240, 244, 247, 248, 249, 250, 251,253, 255, 256, 257, 258, 259, 260, 261, 262, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 283, 290,292, 293, 296, 300, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312,313, 314, 315, 317, 319, 322, 326, 327, 329, 330, 331, 332, 333, 334,338, 339, 340, 340, 341, 342, 344, 350, 351, 352, 353, 355, 356, 357,358, 359, 360, 362, 364, 365, 366, 367, 368, 369, 373, 374, 375, 376,377, 381, 382, 383, 384, 385, 386, 388, 390, 391, 392, 394, 395, 396,400, 403, 404, 405, 406, 407, 408, 409, 410, 411, 413, 414, 415, 417,418, 419, 420, 421, 422, 423, 425, 426, 427, 428, 429, 430, 431, 433,434, 435, 436, 437, 438, 441, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 457, 458, 459, 460, 461, 462, 463, 464,465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,479, 480, 482, 483, 485, 486, 487, 488, 490, 491, 492, 493, 495, 497,498, 499, 500, 501, 503, 504, 505, 506, 507, 508, 509, 516, 517, 521,522, 523, 524, 525, 527, 528, 529, 530, 531, 532, 533, 536, 537, 538,539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552,553, 554, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567,568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 581, 582,583, 584, 586, 587, 588, 589, 590, 591, 594, 596, 597, 598, 600, 601,602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615,616, 617, 618, 619, 620, 622, 623, 624, 626, 627, 628, 629, 632, 633,634, 635, 636, 638, 639, 641, 642, 645, 646, 647, 648, 649, 650, 651,652, 653, 655, 657, 658, 660.

For the following examples, the EC₅₀ was <1 ppm: 3, 11, 19, 49, 55, 62,63, 66, 67, 70, 71, 72, 75, 86, 90, 93, 94, 95, 99-1, 100, 102, 104,105, 116, 135, 136, 137, 148, 182, 183, 184, 193, 195, 199, 213, 216,230, 241, 242, 243, 245, 246, 252, 254, 263, 282, 288, 289, 291, 292,294, 295, 299, 316, 320, 321, 323, 325, 343, 345, 348, 354, 361, 370,371, 372, 373, 378, 379, 380, 401, 416, 424, 440, 456, 580, 585, 621,630, 654.

For the following examples, the EC₅₀ was <10 ppm: 2, 9, 13, 14, 18, 20,21, 27, 28, 59, 67, 68, 78, 87, 88, 91, 92, 96, 99-2, 106, 113, 114,118, 120, 122, 123, 126, 131, 149, 198, 202, 264, 284, 285, 286, 287,288, 301, 302, 318, 324, 328, 335, 336, 337, 346347, 349, 363, 387, 389,393, 397, 398, 399, 402, 412, 432, 439, 481, 484, 485, 489, 491, 492,494, 510, 511, 512, 513, 514, 515, 518, 519, 520, 526, 534, 535, 555,595, 599, 625, 631, 637, 640, 643, 644, 656, 659.

In Vitro Assay 4: Dirofilaria immitis (DIROIM L4)

10 Dirofilaria immitis third-stage larvae, which were freshly isolatedfrom their vector (intermediate host), were added to wells of amicrotitre plate containing a nutrient medium and the test compound inDMSO. Compounds were tested in concentration-response assay induplicate. Larvae exposed to DMSO and no test compounds were used asnegative controls. Larvae were evaluated after 72 h of incubation withthe compound. Within these 72 h of incubation the majority of larvae innegative control moult to fourth-stage larvae. Efficacy was determinedas the reduction of motility in comparison to the negative control.Based on the evaluation of a wide concentration range,concentration-response curves as well as EC₅₀-values were calculated.

For the following examples, the EC₅₀ was <0.1 ppm: 7, 8, 9, 10, 11, 12,13, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34,35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 69, 73, 74, 75, 76,77, 81, 82, 83, 89, 101, 108, 112, 117, 119, 124, 125, 127, 130, 132,133, 134, 138, 139, 140, 141, 142, 143, 144, 146, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 174, 175, 176, 177, 178, 179, 181, 186, 190, 191,192, 194, 196, 197, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211,212, 214, 215, 217, 218, 220, 221, 222, 223, 224, 225, 226, 227, 228,229, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 247, 248, 249,250, 251, 253, 256, 257, 258, 259, 260, 261, 262, 265, 267, 268, 271,272, 275, 277, 278, 279, 280, 281, 283, 290, 300, 304, 309, 310, 313,314, 315, 319, 322, 326, 327, 330, 331, 332, 333, 334, 336, 338, 339,340, 341, 350, 351, 352, 353, 355, 356, 357, 358, 359, 360, 362, 365,366, 367, 374, 376, 377, 382, 384, 385, 386, 388, 390, 392, 394, 395,396, 400, 403, 404, 405, 406, 407, 408, 409, 410, 411, 413, 414, 415,417, 418, 419, 420, 421, 422, 423, 425, 426, 427, 429, 430, 431, 433,434, 436, 437, 438, 441, 442, 443, 444, 446, 447, 448, 449, 450, 451,452, 453, 454, 455, 457, 462, 463, 465, 466, 467, 468, 469, 470, 476,477, 478, 479, 480, 482, 485, 486, 487, 488, 490, 491, 492, 493, 495,496, 497, 498, 499, 504, 505, 506, 507, 516, 517, 523, 525, 527, 528,529, 530, 531, 532, 533, 536, 537, 538, 539, 540, 541, 542, 543, 544,545, 548, 549, 550, 551, 552, 553, 554, 556, 557, 558, 559, 561, 562,563, 564, 565, 566, 567, 568, 570, 571, 572, 573, 575, 576, 577, 578,579, 582, 583, 584, 587, 589, 590, 591, 596, 597, 600, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 617, 618, 619,628, 629, 635, 638, 660.

For the following examples, the EC₅₀ was <1 ppm: 1, 2, 3, 14, 20, 54,80, 115, 150, 201, 244, 266, 364, 373.

For the following examples, the EC₅₀ was <10 ppm: 133, 187

In Vitro Assay 5: Litomosoides sigmodontis (LTMOSI L3)

10 Litomosoides sigmodontis third-stage larvae, which were freshlyisolated from the pleural cavity of an infected rodent, were added towells of a microtitre plate containing a nutrient medium and the testcompound in DMSO. Compounds were tested in concentration-response assayin duplicate. Larvae exposed to DMSO and no test compounds were used asnegative controls. Larvae were evaluated after 72 h of incubation withthe compound. Efficacy was determined as the reduction of motility incomparison to the negative control. Based on the evaluation of a wideconcentration range, concentration-response curves as well asEC₅₀-values were calculated.

For the following examples, the EC₅₀ was <0.1 ppm: 8, 9, 10, 12, 13, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 29, 32, 33, 34, 35, 36, 37, 45, 46,48, 52, 53, 54, 74, 76, 77, 112, 133, 134, 141, 143, 339, 341, 350, 376,382, 384, 385, 386, 394, 395, 396.

For the following examples, the EC₅₀ was <1 ppm: 3, 15, 44, 73, 373.

In Vitro Assay 6: Cooperia curticei (COOPCU L3)

Solvent: Dimethyl Sulfoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are dissolved in 0.5 ml solvent, and the concentrate is dilutedwith “Ringer's solution” to the desired concentration.

Approximately 40 nematode larvae (Cooperia curticei) are transferredinto a test tube containing the compound solution.

After 5 days percentage of larval mortality is recorded. 100% efficacymeans all larvae are killed; 0% efficacy means no larvae are killed.

In this test for example, the following compounds from the preparationexamples showed good activity of 100% at an application rate of 20 ppm:8, 9, 10, 13, 17, 22, 23, 24, 29, 32, 33, 34, 36, 37, 45, 46, 52, 53,57, 76, 77, 81, 83, 132, 133, 134, 139, 143, 150, 153, 155, 156, 157,166, 167, 169, 170, 172, 191, 192, 193, 194, 195, 196, 197, 200, 204,205, 206, 207, 208, 209, 210, 214, 215, 217, 218, 221, 222, 224, 226,235, 236, 237, 247, 265, 266, 274, 280, 300, 309, 326, 327, 329, 332,341, 350, 353, 356, 357, 359, 373, 377, 384, 385, 386, 395, 396, 407,408, 410, 411, 415, 419, 420, 421, 426, 431, 438, 445, 449, 450, 451,453, 454, 455, 464, 477, 479, 486, 487, 488, 496, 497, 504, 505, 506,507, 516, 528, 529, 530, 531, 532, 533, 536, 537, 538, 539, 541, 542,545, 551, 554, 557, 558, 562, 563, 564, 565, 569, 572, 573, 575, 576,596, 600, 603, 604, 605, 607, 608, 624, 628, 631, 637, 638, 639, 642,647, 651, 652, 655, 657, 658, 659, 660.

In this test for example, the following compounds from the preparationexamples showed good activity of 90% at an application rate of 20 ppm:16, 31, 40, 48, 50, 54, 60, 80, 108, 125, 142, 152, 176, 178, 179, 191,201, 203, 220, 223, 229, 240, 251, 257, 259, 260, 271, 275, 276, 281,292, 314, 330, 331, 333, 338, 339, 358, 382, 400, 406, 435, 444, 446,462, 465, 467, 469, 473, 476, 491, 500, 509, 540, 543, 548, 552, 553,601, 602, 615, 640, 648.

In this test for example, the following compounds from the preparationexamples showed good activity of 80% at an application rate of 20 ppm:15, 21, 30, 41, 42, 44, 47, 49, 51, 58, 65, 70, 75, 89, 135, 146, 154,162, 163, 181, 211, 212, 228, 238, 239, 250, 272, 294, 298, 307, 310,315, 318, 322, 328, 367, 394, 404, 409, 418, 424, 432, 460, 471, 482,485, 490, 492, 495, 508, 556, 583, 587, 614, 650.

In this test for example, the following compounds from the preparationexamples showed good activity of 100% at an application rate of 4 ppm:8, 13, 17, 22, 23, 24, 32, 33, 34, 36, 37, 45, 46, 52, 53, 57, 76, 77,81, 83, 132, 133, 134, 143, 151, 153, 155, 167, 169, 170, 172, 192, 194,195, 197, 200, 205, 207, 209, 210, 214, 215, 217, 222, 226, 237, 265,266, 273, 274, 300, 309, 327, 329, 332, 350, 353, 359, 373, 384, 385,386, 395, 395, 396, 407, 408, 410, 411, 415, 420, 421, 426, 431, 438,445, 449, 450, 451, 453, 455, 477, 479, 487, 488, 496, 497, 499, 504,505, 529, 530, 531, 532, 533, 536, 539, 541, 542, 545, 554, 557, 558,562, 563, 564, 565, 569, 572, 573, 575, 576, 596, 600, 604, 607, 608,628, 631, 637, 638, 639, 642, 647, 651, 652, 655, 657, 658, 659, 660.

In this test for example, the following compounds from the preparationexamples showed good activity of 90% at an application rate of 4 ppm: 9,29, 31, 40, 54, 60, 125, 139, 142, 152, 156, 157, 166, 191, 193, 196,208, 218, 221, 223, 229, 235, 236, 247, 271, 275, 292, 326, 330, 338,341, 356, 357, 358, 419, 435, 446, 462, 464, 469, 476, 500, 506, 507,540, 551, 552, 601, 603, 605, 648.

In this test for example, the following compounds from the preparationexamples showed good activity of 80% at an application rate of 4 ppm:10, 16, 39, 42, 44, 47, 48, 50, 51, 58, 80, 108, 146, 163, 171, 178,201, 203, 206, 211, 212, 224, 240, 258, 260, 280, 281, 286, 318, 333,339, 400, 406, 409, 430, 437, 444, 465, 467, 486, 491, 508, 509, 516,528, 537, 548, 583, 602, 614, 624, 640.

In this test for example, the following compounds from the preparationexamples showed good activity of 80% at an application rate of 0.8 ppm:190, 549.

In Vitro Assay 7: Haemonchus contortus (HAEMCO L3)

Solvent: Dimethyl Sulfoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are dissolved in 0.5 ml solvent, and the concentrate is dilutedwith “Ringer's solution” to the desired concentration.

Approximately 40 larvae of the red stomach worm (Haemonchus contortus)are transferred into a test tube containing compound solution.

After 5 days the percentage of larval mortality is recorded. 100%efficacy means all larvae are killed, 0% efficacy means no larvae arekilled.

In this test for example, the following compounds from the preparationexamples showed good activity of 100% at an application rate of 20 ppm:8, 13, 15, 17, 22, 23, 24, 29, 32, 33, 34, 36, 37, 46, 47, 48, 50, 52,53, 57, 60, 76, 77, 81, 83, 132, 133, 134, 135, 139, 142, 143, 153, 155,166, 167, 169, 170, 172, 192, 194, 197, 200, 205, 206, 207, 214, 215,218, 221, 222, 224, 226, 235, 237, 247, 265, 266, 274, 275, 280, 300,309, 312, 326, 329, 330, 331, 332, 350, 353, 359, 373, 377, 384, 385,386, 395, 396, 407, 410, 411, 415, 450, 455, 477, 486, 487, 488, 496,497, 504, 505, 506, 509, 528, 529, 530, 531, 533, 537, 538, 539, 541,542, 545, 551, 552, 554, 558, 562, 563, 564, 565, 569, 572, 573, 575,576, 596, 604, 605, 608, 628, 631, 637, 638, 647, 651, 652, 655, 658,659, 660.

In this test for example, the following compounds from the preparationexamples showed good activity of 90% at an application rate of 20 ppm:10, 31, 44, 45, 51, 74, 75, 136, 146, 150, 156, 179, 191, 203, 204, 209,210, 217, 220, 223, 229, 236, 249, 250, 251, 258, 260, 271, 272, 327,356, 357, 358, 400, 408, 421, 435, 438, 444, 445, 449, 451, 453, 460,469, 476, 508, 532, 540, 548, 553, 557, 600, 602, 603, 615, 640, 642,648, 657.

In this test for example, the following compounds from the preparationexamples showed good activity of 80% at an application rate of 20 ppm:12, 16, 39, 40, 42, 70, 125, 137, 138, 152, 157, 176, 178, 180, 208,257, 259, 273, 276, 281, 292, 307, 310, 333, 341, 388, 392, 394, 419,420, 432, 434, 446, 464, 473, 479, 491, 499, 500, 507, 516, 535, 543,619, 624, 645, 646, 650.

In this test for example, the following compounds from the preparationexamples showed good activity of 100% at an application rate of 4 ppm:8, 9, 13, 17, 22, 23, 24, 29, 32, 34, 36, 37, 40, 46, 52, 57, 60, 76,77, 81, 132, 133, 134, 139, 142, 143, 153, 155, 170, 192, 197, 200, 205,214, 222, 237, 247, 265, 266, 274, 309, 330, 332, 339, 350, 359, 373,384, 385, 386, 395, 410, 411, 455, 477, 488, 496, 497, 504, 509, 530,531, 539, 541, 542, 545, 554, 558, 562, 563, 564, 565, 569, 572, 573,575, 576, 596, 605, 608, 628, 631, 637, 639, 647, 651, 652, 655, 658,659, 660.

In this test for example, the following compounds from the preparationexamples showed good activity of 90% at an application rate of 4 ppm:10, 15, 31, 33, 45, 47, 50, 83, 135, 146, 151, 166, 167, 169, 191, 194,207, 209, 221, 226, 229, 235, 236, 271, 272, 275, 300, 326, 329, 353,357, 358, 396, 400, 407, 408, 415, 421, 435, 436, 438, 445, 450, 451,476, 487, 505, 508, 528, 529, 533, 536, 537, 540, 552, 600, 603, 604,638, 640, 648.

In this test for example, the following compounds from the preparationexamples showed good activity of 80% at an application rate of 4 ppm:42, 44, 48, 51, 53, 74, 75, 150, 156, 172, 195, 206, 210, 215, 217, 218,223, 232, 260, 281, 307, 327, 341, 356, 377, 392, 394, 403, 419, 42,426, 444, 449, 453, 469, 470, 471, 479, 486, 500, 506, 507, 551, 557,642, 645, 650, 657.

FORMULATION EXAMPLE

Exemplary formulations consisted of the active substance in 10%Transcutol, 10% Cremophor EL and 80% isotonic saline solution. First theactive substance was dissolved in Transcutol. After solution inTranscutol, Cremophor and isotonic saline solution were added. Theseformulations were used as service formulations in the following in vivoassay.

An example for a formulation according to the present invention is thefollowing formulation Example F1. Therein, the active substance wasdissolved in Transcutol to form a stock solution A. Then 0.100 mL ofthis stock solution A were taken and 0.100 mL Cremophor EL and 0.800 mLisotonic saline solution were added. The resulting liquid formulation(formulation example F1) had a volume of 1 mL.

Stock Solution A:

 4.0 mg compound of example 8, 0.100 mL Transcutol.

Formulation Example F1

0.100 mL stock solution A, 0.100 mL Cremophor EL, and 0.800 mL isotonicsaline solution.

In Vivo Assay

Haemonchus contortus/Trichostrongylus colubriformis/Gerbil

Gerbils, experimentally infected with Haemonchus and/orTrichostrongylus, were treated once during late prepatency. Testcompounds were formulated as solutions or suspensions and applied orallyor intraperitoneally. For both applications the same service formulationwas used. The volume of the application amounted to normally 20 ml/kg ata maximum. By way of example, a gerbil with 40 g body weight was treatedwith 0.200 mL of the formulation of formulation example F1. Thiscorresponded to a treatment with 20 mg/kg body weight.

Efficacy was determined per group as reduction of worm count in stomachand small intestine, respectively, after necropsy compared to worm countin an infected and placebo-treated control group.

The following examples were tested and had an activity of >70% or higherat the given treatment:

Treatment Haemonchus contortus Trichostrongylus colubriformis ≤2.5 mg/kgExpl No 8, 9, 13, 15, 17, 18, 21, 22, Expl No 8, 13, 17, 22, 37, 51, 52,intraperitoneally 23, 24, 25, 33, 34, 36, 37, 44, 46, 132, 133, 134,142, 143, 168, 169, 52, 54, 130, 153, 156, 166, 167, 170, 200 206, 222,235, 251, 359, 168, 181, 192, 200, 201, 203, 205, 395, 660 206, 209,214, 220, 221, 222, 232, 233, 234, 235, 237, 238, 239, 250, 251, 300,301, 309, 310, 322, 326, 327, 330, 331, 355, 357, 358, 359, 360, 374,385, 386, 392, 395, 409, 410, 411, 413, 415, 419, 427, 430, 431, 438,444, 450, 455 462, 465, 467, 468, 477, 485, 487, 491, 492, 496, 516,530, 533, 538, 540, 543, 548, 553, 557, 558, 564, 565, 660

The invention claimed is:
 1. A compound of formula (I):

wherein: A is A2,

is 0, 1, 2, 3 or 4, R is selected from the group consisting of hydrogen,halogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂-C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl, —S(O)-C₁-C₄-halogenoalkyl and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R_(p) is selectedfrom the group consisting of hydrogen and C₁-C₄-alkyl, X, Y areindependently selected from the group consisting of CR⁷R⁸, O, S, andN—R⁹, wherein at least one of X and Y is CR⁷R⁸, or X, Y form together aring member selected from the group consisting of —C(O)—O—, —C(O)—NR⁹—,—S(O)—NR⁹—, —SO₂—NR⁹— and —SO₂—O—, R¹ is selected from the groupconsisting of hydrogen, cyano, —CHO, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,C₃-C₆-halogenocycloalkyl having 1 to 5 halogen atoms, C₃-C₄-alkenyl,C₃-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-C₁-C₃-alkyl,cyano-C₁-C₄-alkyl, —NH-C₁-C₄-alkyl, —N(C₁-C₄-alkyl)₂, NH₂-C₁-C₄-alkyl-,C₁-C₄-alkyl-NH-C₁-C₄-alkyl-, (C₁-C₄-alkyl)₂N-C₁-C₄-alkyl-,C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl-C(O)— having 1 to 5 halogenatoms, C₁-C₄-alkoxy-C(O)—, benzyloxy-C(O)—,C₁-C₄-alkoxy-C₁-C₄-alkyl-C(O)—, —SO₂—C₁-C₄-alkyl,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,phenyl-C₁-C₄-alkyl, optionally substituted by 1, 2, 3, 4 or 5substituents independently selected from the group consisting ofhalogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂-C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, andheterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, —OH, —NO₂,cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R² is selectedfrom the group consisting of hydrogen, halogen, cyano, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),—C(O)—N(C₁-C₄-alkyl)₂, —NR¹²R¹³, —OR¹⁴, —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵,C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl,C₂-C₄-alkynyl, phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₆-alkyl,C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl, andphenyl-C₁-C₄-alkyl is optionally substituted by 1, 2, 3, 4 or 5substituents independently selected from the group consisting ofhalogen, —OH, —NO₂, cyano, C₁-C₄-alkyl-C(O)—, C₁-C₄-alkoxy-C(O)-,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —NH(C(O)—C₁-C₄-alkyl),—N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, —OH, —NO₂,cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, cyano, nitro, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-memberedheteroaryl and 6-membered heteroaryl, each of which is optionallysubstituted by 1, 2, 3 or 4 substituents independently selected from thegroup consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),—C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-, C₁-C₄-halogenoalkoxyhaving 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and 4- to10-membered heterocycloalkyl, R³ is hydrogen or C₁-C₄-alkyl, R⁴ isselected from the group consisting of hydrogen, halogen, —OH, cyano,C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxyhaving 1 to 5 halogen atoms, C₁-C₄-alkyl-C(O)—, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, and—SO₂—C₁-C₄-alkyl, R⁵ is selected from the group consisting of hydrogen,halogen, —OH, cyano, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₁-C₄-alkyl-C(O)—,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, and —SO₂—C₁-C₄-alkyl, R⁶ is selected from the groupconsisting of hydrogen, halogen, —OH, cyano, C₁-C₄-alkyl,C₃-C₆-cycloalkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to5 halogen atoms, C₁-C₄-alkyl-C(O)—, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, and—SO₂—C₁-C₄-alkyl, R⁷ is selected from the group consisting of hydrogen,—OH, fluorine, C₁-C₄-alkyl and C₁-C₄-alkoxy, R⁸ is selected from thegroup consisting of hydrogen, —OH, fluorine, C₁-C₄-alkyl andC₁-C₄-alkoxy, or R⁷ and R⁸ together form an oxo group (═O), or R⁷ and R⁸form, together with the carbon atom to which they are attached, a 3- to6-membered ring selected from the group consisting of C₃-C₆-cycloalkyland 3- to 6-membered heterocycloalkyl, R⁹ is selected from the groupconsisting of hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms and C₁-C₄-alkoxy, R¹² and R¹³ are independently selectedfrom the group consisting of hydrogen, —OH, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —NH(—C(O)—C₁-C₄-alkyl),—N(C₁-C₄-alkyl)(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy, C₁-C₄-alkoxy-C(O)—,C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, wherein each of theC₁-C₄-alkyl, C₃-C₆-cycloalkyl, and phenyl-C₁-C₄-alkyl is optionallysubstituted by 1, 2 or 3 substituents independently selected from thegroup consisting of halogen, —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂,—NH—C(O)—C₁-C₄-alkyl, —N(C₁-C₄-alkyl)(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and(C₁-C₄-alkoxy)₂P(═O)—, heterocyclyl-C₁-C₄-alkyl, wherein theheterocyclyl substituent is selected from the group consisting of 4- to10-membered heterocycloalkyl, 5-membered heteroaryl and 6-memberedheteroaryl, each of which is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl,benzo-C₅-C₆-cycloalkyl, wherein each of the phenyl andbenzo-C₅-C₆-cycloalkyl is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and a monocyclicor a bicyclic heterocycle selected from the group of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R¹⁴ is selectedfrom the group consisting of —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, wherein each of theC₁-C₄-alkyl, C₃-C₆-cycloalkyl, and phenyl-C₁-C₄-alkyl is optionallysubstituted by 1, 2 or 3 substituents independently selected from thegroup consisting of halogen, —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl, which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, cyano, nitro, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and6-membered heteroaryl, each of which is optionally substituted by 1, 2or 3 substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂-C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R¹⁵ is selectedfrom the group consisting of hydrogen, C₁-C₄-alkyl, C₃-C₆-cycloalkyl,phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₄-alkyl, C₃-C₆-cycloalkyl,and phenyl-C₁-C₄-alkyl is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl, which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, cyano, nitro, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and6-membered heteroaryl, each of which is optionally substituted by 1, 2or 3 substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, Q is selected fromthe group consisting of 6- or 10-membered aryl and 5- to 10-memberedheteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5substituents selected from the group consisting of halogen, SF₅, cyano,—CHO, nitro, oxo, C₁-C₄-alkyl, C₁-C₄-hydroxyalkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, hydroxy, C₁-C₄-alkoxy,C₃-C₆-cycloalkyl-C₁-C₄-alkoxy, cyano-C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxyhaving 1 to 5 halogen atoms, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—NH—SO₂—(C₁-C₄-alkyl), —N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl),(C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4- to 6-membered heterocyclyl, which isoptionally substituted with 1 or 2 substituents selected from the groupconsisting of fluorine, chlorine, bromine, methyl and cyano,—CH₂—O—(C₁-C₄-alkyl), —CH₂—NH(C₁-C₄-alkyl), —CH₂—N(C₁-C₄-alkyl)₂, methylsubstituted with a 4- to 6-membered heterocyclyl which itself isoptionally substituted with 1 or 2 substituents selected from the groupconsisting of fluorine, chlorine, bromine, methyl and cyano,—CH₂—S—(C₁-C₄-alkyl), —CH₂—S(O)—(C₁-C₄-alkyl), —CH₂—SO₂—(C₁-C₄-alkyl),—S—(C₁-C₄-alkyl), —S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl),—S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),—NHCO(C₃-C₆-cycloalkyl), and —NHCO(C₁-C₄-halogenoalkyl) having 1 to 5halogen atoms, wherein when Y is O, S or N—R⁹, none of R⁷ and R⁸ is —OH,and wherein when X is O, S or N—R⁹, none of R⁷ and R⁸ is —OH, or astereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a saltthereof, or a mixture of any of the foregoing.
 2. The compound accordingto claim 1, wherein: A is A2,

is 0, 1, 2, 3 or 4, R is selected from the group consisting of hydrogen,halogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl, —S(O)—C₁-C₄-halogenoalkyl and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R_(p) is selectedfrom the group consisting of hydrogen and C₁-C₄-alkyl, X, Y areindependently selected from the group consisting of CR⁷R⁸, O, S, andN—R⁹, wherein at least one of X and Y is CR⁷R⁸, or X, Y form together aring member selected from the group consisting of —C(O)—O—, —C(O)—NR⁹—,—S(O)—NR⁹—, —SO₂—NR⁹— and —SO₂—O—, R¹ is selected from the groupconsisting of hydrogen, cyano, —CHO, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,C₃-C₆-halogenocycloalkyl having 1 to 5 halogen atoms, C₃-C₄-alkenyl,C₃-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-C₁-C₃-alkyl,cyano-C₁-C₄-alkyl, —NH-C₁-C₄-alkyl, —N(C₁-C₄-alkyl)₂, NH₂-C₁-C₄-alkyl-,C₁-C₄-alkyl-NH-C₁-C₄-alkyl-, (C₁-C₄-alkyl)₂N-C₁-C₄-alkyl-,C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl-C(O)— having 1 to 5 halogenatoms, C₁-C₄-alkoxy-C(O)—, benzyloxy-C(O)—,C₁-C₄-alkoxy-C₁-C₄-alkyl-C(O)—, —SO₂—C₁-C₄-alkyl,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,phenyl-C₁-C₄-alkyl, optionally substituted by 1, 2, 3, 4 or 5substituents independently selected from the group consisting ofhalogen, —OH, —NO₂, cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, andheterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, —OH, —NO₂,cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R² is selectedfrom the group consisting of hydrogen, halogen, cyano, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),—C(O)—N(C₁-C₄-alkyl)₂, —NR¹²R¹³, —OR¹⁴, —SR¹⁵, —S(O)R¹⁵, —SO₂R¹⁵,C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl,C₂-C₄-alkynyl phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₆-alkyl,C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl andphenyl-C₁-C₄-alkyl is optionally substituted by 1, 2, 3, 4 or 5substituents independently selected from the group consisting ofhalogen, —OH, —NO₂, cyano, C₁-C₄-alkyl-C(O)—, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy, —NH₂,“—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —NH(C(O)—C₁-C₄-alkyl),—N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, —OH, —NO₂,cyano, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, cyano, nitro, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-memberedheteroaryl and 6-membered heteroaryl, each of which is optionallysubstituted by 1, 2, 3 or 4 substituents independently selected from thegroup consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),—C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-, C₁-C₄-halogenoalkoxyhaving 1 to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and 4- to10-membered heterocycloalkyl, R³ is hydrogen, or C₁-C₄-alkyl, R⁴ isselected from the group consisting of hydrogen, halogen, —OH, cyano,C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, R⁵ is selected from the groupconsisting of hydrogen, halogen, —OH, cyano, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, R⁶ is selected from the groupconsisting of hydrogen, halogen, —OH, cyano, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, R⁷ is selected from the groupconsisting of hydrogen, —OH, fluorine, C₁-C₄-alkyl and C₁-C₄-alkoxy, R⁸is selected from the group consisting of hydrogen, —OH, fluorine,C₁-C₄-alkyl and C₁-C₄-alkoxy, or R⁷ and R⁸ together form an oxo group(═O), R⁹ is selected from the group consisting of hydrogen, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and C₁-C₄-alkoxy, R¹²and R¹³ are independently selected from the group consisting ofhydrogen, —OH, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy, C₁-C₄-alkyl, C₃-C₆-cycloalkyl,phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₄-alkyl, C₃-C₆-cycloalkyl,and phenyl-C₁-C₄-alkyl is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, —NH—C(O)—C₁-C₄-alkyl,—N(C₁-C₄-alkyl)+C(O)—C₁-C₄-alkyl), C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and(C₁-C₄-alkoxy)₂P(═O)—, heterocyclyl-C₁-C₄-alkyl, wherein theheterocyclyl substituent is selected from the group consisting of 4- to10-membered heterocycloalkyl, 5-membered heteroaryl and 6-memberedheteroaryl, each of which is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl,benzo-C₅-C₆-cycloalkyl, wherein each of the phenyl andbenzo-C₅-C₆-cycloalkyl is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and a monocyclicor a bicyclic heterocycle selected from the group of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R¹⁴ is selectedfrom the group consisting of —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, wherein each of theC₁-C₄-alkyl, C₃-C₆-cycloalkyl, and phenyl-C₁-C₄-alkyl which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, —OH, cyano, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),—C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogenatoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl, which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, cyano, nitro, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and6-membered heteroaryl, each of which is optionally substituted by 1, 2or 3 substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, R¹⁵ is selectedfrom the group consisting of hydrogen, C₁-C₄-alkyl, C₃-C₆-cycloalkyl,phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₄-alkyl, C₃-C₆-cycloalkyl,and phenyl-C₁-C₄-alkyl which is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, —OH, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,heterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, phenyl, which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, cyano, nitro, —OH, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to5 halogen atoms, —S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atomsand —SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and6-membered heteroaryl, each of which is optionally substituted by 1, 2or 3 substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,hydroxy-C₁-C₄-alkyl, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, Q is a substitutedphenyl ring of formula (Q1)

wherein: Z¹, Z², Z³, Z⁴, and Z⁵ are independently selected from thegroup consisting of hydrogen, halogen, SF₅, cyano, —CHO, nitro,C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, hydroxy,C₁-C₄-alkoxy, C₃-C₆-cycloalkyl-C₁-C₄-alkoxy, cyano-C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —NH—SO₂—(C₁-C₄-alkyl),—N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl), (C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4-to 6-membered heterocyclyl, which is optionally substituted with 1 or 2substituents selected from the group consisting of fluorine, chlorine,bromine, methyl and cyano, —CH₂—O—(C₁-C₄-alkyl), —CH₂—NH(C₁-C₄-alkyl),—CH₂—N(C₁-C₄-alkyl)₂, methyl substituted with a 4- to 6-memberedheterocyclyl which itself is optionally substituted with 1 or 2substituents selected from the group consisting of fluorine, chlorine,bromine, methyl and cyano, —CH₂—S—(C₁-C₄-alkyl),—CH₂—S(O)—(C₁-C₄-alkyl), —CH₂—SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-alkyl),—S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-halogenoalkyl) having1 to 5 halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogenatoms, —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),—NHCO(C₃-C₆-cycloalkyl), and —NHCO(C₁-C₄-halogenoalkyl) having 1 to 5halogen atoms, or Z¹ and Z² form, together with the carbon atoms thatthey are connected to, a 5- or 6-membered saturated or partiallysaturated heterocyclic ring, a 5-membered heteroaryl, or a 6-memberedheteroaryl, each of which may be optionally substituted with one or twosubstituents selected from the group consisting of methyl, fluorine andoxo, and Z³, Z⁴, and Z⁵ are independently selected from the groupconsisting of hydrogen, halogen, SF₅, cyano, CHO, nitro, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C₁-C₄-alkoxy,C₃-C₆-cycloalkyl-C₁-C₄-alkoxy, cyano-C₁-C₄-alkoxy, C₁-C₄-alkoxy-C(O)—,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —NH—SO₂—(C₁-C₄-alkyl),—N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl), (C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4-to 6-membered heterocycloalkyl which is optionally substituted with 1 or2 substituents selected from the group consisting of fluorine, methyl orcyano, —CH₂—O—(C₁-C₄-alkyl), —CH₂—NH(C₁-C₄-alkyl), —CH₂—N(C₁-C₄-alkyl)₂,methyl substituted with a 4- to 6-membered heterocycloalkyl which itselfis optionally substituted with 1 or 2 substituents selected from thegroup consisting of fluorine, methyl or cyano, —CH₂—S—(C₁-C₄-alkyl),—CH₂—S(O)-(C₁-C₄-alkyl), —CH₂—SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-alkyl),—S(O)—(C₁-C₄-alkyl), —SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-halogenoalkyl) having1 to 5 halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogenatoms, —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),—NHCO(C₃-C₆-cycloalkyl), and —NHCO(C₁-C₄-halogenoalkyl) having 1 to 5halogen atoms, or Z² and Z³ form, together with the carbon atoms thatthey are connected to, a 5- or 6-membered saturated or partiallysaturated heterocyclic ring, a 5-membered heteroaryl, or a 6-memberedheteroaryl, each of which may be optionally substituted with one or twosubstituents selected from the group consisting of methyl, fluorine andoxo, and Z¹, Z⁴, and Z⁵ are independently selected from the groupconsisting of hydrogen, halogen, SF₅, cyano, CHO, nitro, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C₁-C₄-alkoxy,C₃-C₆-cycloalkyl-C₁-C₄-alkoxy, cyano-C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxyhaving 1 to 5 halogen atoms, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—NH—SO₂—(C₁-C₄-alkyl), —N(SO₂—[C₁-C₄-alkyl])(C₁-C₄-alkyl),(C₁-C₄-alkoxyimino)-C₁-C₄-alkyl, 4- to 6-membered heterocycloalkyl whichis optionally substituted with 1 or 2 substituents selected from thegroup consisting of fluorine, methyl or cyano, —CH₂—O—(C₁-C₄-alkyl),—CH₂—NH(C₁-C₄-alkyl), —CH₂—N(C₁-C₄-alkyl)₂, methyl substituted with a 4-to 6-membered heterocycloalkyl which itself is optionally substitutedwith 1 or 2 substituents selected from the group consisting of fluorine,methyl or cyano, —CH₂—S—(C₁-C₄-alkyl), —CH₂—S(O)-(C₁-C₄-alkyl),—CH₂—SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-alkyl), —S(O)—(C₁-C₄-alkyl),—SO₂—(C₁-C₄-alkyl), —S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogenatoms, —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—CONH(C₁-C₄-alkyl), —CONH(C₃-C₆-cycloalkyl), —NHCO(C₁-C₄-alkyl),—NHCO(C₃-C₆-cycloalkyl), and —NHCO(C₁-C₄-halogenoalkyl) having 1 to 5halogen atoms, or Q is a pyridine ring of formula (Q2)

wherein: Z⁶, Z⁷, Z⁸ and Z⁹ are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, or Q is apyrimidine ring of formula (Q3)

wherein: Z¹⁰, Z¹¹ and Z¹² are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, or Q is apyridine ring of formula (Q4)

wherein: Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the groupconsisting of hydrogen halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —NH—CO-C₁-C₄-alkyl, and monocyclic heterocyclesselected from the group of 4- to 7-membered heterocycloalkyl or5-membered heteroaryls having at least one nitrogen atom via which theheteroaryl ring is connected to the pyridine ring, each of which isoptionally substituted with 1, 2 or 3 substituents independentlyselected from the group consisting of halogen, cyano, nitro, —OH, oxo,thiono, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, and—SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or Q is apyridine ring of formula (Q5)

wherein: Z¹⁷, Z¹⁸, Z¹⁹ and Z²⁰ are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, or Q is a5-membered aromatic heterocycle of formula (Q6)

wherein: T¹-T⁴are independently selected from the group consisting of N,O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O, not morethan one of T¹-T⁴ is S, not more than one of T¹-T⁴ is N—Z²², and whereineach Z²¹ is independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, and each Z²² is independently selected from the groupconsisting of hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, andC₁-C₄-alkoxy-C₁-C₄-alkyl, or Q is a 5-membered aromatic heterocycle offormula (Q7)

wherein: U¹-U⁴ are independently selected from the group consisting of Nand C-Z²³, wherein not more than three of U¹-U⁴ are N, and wherein eachZ²³ is independently selected from the group consisting of hydrogen,halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5 halogenatoms, wherein when Y is O, S or N—R⁹, none of R⁷ and R⁸ is —OH, andwherein when X is O, S or N—R⁹, none of R⁷ and R⁸ is —OH, or astereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a saltthereof, or a mixture of any of the foregoing.
 3. The compound accordingto claim 1, wherein: A is A2,

o is 0, 1 or 2, R is selected from the group consisting of halogen,C₁-C₄-alkyl, C₁-C₄-alkoxy, cyano, and C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, R_(p) is selected from the group consisting of hydrogenand C₁-C₄-alkyl, X, Y are independently selected from the groupconsisting of CR⁷R⁸, O, S, and N—R⁹, wherein at least one of X and Y isCR⁷R⁸, R¹ is selected from the group consisting of hydrogen,C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₃-C₄-alkenyl, C₃-C₄-alkynyl,C₁-C₄-alkoxy-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-C₁-C₃-alkyl, andcyano-C₁-C₄-alkyl, R² is selected from the group consisting of hydrogen,halogen, cyano, —COOH, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, —NR¹²R¹³, —OR¹⁴, —SR¹⁵,—S(O)R¹⁵, —SO₂R¹⁵, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl, wherein each ofthe C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl,C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl is optionally substituted by 1, 2,3, 4 or 5 substituents independently selected from the group consistingof halogen, —OH, cyano, C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂,—C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy, —NH₂,—NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —NH(C(O)—C₁-C₄-alkyl),—N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl,—SO₂—C₁-C₄-alkyl, —S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and a monocyclicor a bicyclic heterocycle selected from the group consisting of 4- to10-membered heterocycloalkyl, heterospirocycloalkyl, 5-memberedheteroaryl and 6-membered heteroaryl, each of which is optionallysubstituted by 1, 2, 3 or 4 substituents independently selected from thegroup consisting of halogen, cyano, —OH, oxo, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl), —C(O)—N(C₁-C₄-alkyl)₂, C₁-C₄-alkyl,C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl-,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, and 4- to 10-memberedheterocycloalkyl, R³ is hydrogen or C₁-C₄-alkyl, R⁴ is selected from thegroup consisting of hydrogen, halogen, —OH, cyano, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, R⁵ is selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH₂, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, R⁶ isselected from the group consisting of hydrogen, halogen, cyano,C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH₂,—NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, R⁷ is selected from the groupconsisting of hydrogen and C₁-C₄-alkyl, R⁸ is selected from the groupconsisting of hydrogen and C₁-C₄-alkyl, or R⁷ and R⁸ together form anoxo group (═O), R⁹ is C₁-C₄-alkyl, R¹² and R¹³ are independentlyselected from the group consisting of hydrogen, —NH(—C(O)—C₁-C₄-alkyl),C₁-C₄-alkoxy, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, whereineach of the C₁-C₄-alkyl, C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of halogen, —OH, cyano, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—NH(C₁-C₄-alkyl),—C(O)—N(C₁-C₄-alkyl)₂, —NH—C(O)—C₁-C₄-alkyl,—N(C₁-C₄-alkyl)+C(O)—C₁-C₄-alkyl), C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—S(O)—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,—SO₂—C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms and(C₁-C₄-alkoxy)₂P(═O)—, heterocyclyl-C₁-C₄-alkyl, wherein theheterocyclyl substituent is selected from the group consisting of 4- to10-membered heterocycloalkyl, 5-membered heteroaryl and 6-memberedheteroaryl, each of which is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogenatoms, phenyl, benzo-C₅-C₆-cycloalkyl, wherein each of the phenyl andbenzo-C₅-C₆-cycloalkyl is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5 halogenatoms, and a monocyclic or a bicyclic heterocycle selected from thegroup of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and6-membered heteroaryl, each of which is optionally substituted by 1, 2or 3 substituents independently selected from the group consisting ofhalogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, R¹⁴ is selected from the group consisting of C₁-C₄-alkyl,C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₄-alkyl,C₃-C₆-cycloalkyl, and phenyl-C₁-C₄-alkyl is optionally substituted by 1,2 or 3 substituents independently selected from the group consisting ofhalogen, —OH, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogenatoms, and C₃-C₆-cycloalkyl, and heterocyclyl-C₁-C₄-alkyl, wherein theheterocyclyl substituent is selected from the group consisting of 4- to10-membered heterocycloalkyl, 5-membered heteroaryl and 6-memberedheteroaryl, each of which is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, R¹⁵ is selected from the group consisting of hydrogen,C₁-C₄-alkyl, phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₄-alkyl andphenyl-C₁-C₄-alkyl is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, —OH, cyano,C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, andheterocyclyl-C₁-C₄-alkyl, wherein the heterocyclyl substituent isselected from the group consisting of 4- to 10-memberedheterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, eachof which is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, cyano,C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, Q isa substituted phenyl ring of formula (Q1)

wherein: Z¹, Z², Z³, Z⁴, and Z⁵ are independently selected from thegroup consisting of hydrogen, halogen, cyano, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, 4- to 6-membered heterocyclyl, which is optionallysubstituted with 1 or 2 substituents selected from the group consistingof fluorine, chlorine, bromine, methyl and cyano, —S—(C₁-C₄-alkyl),—S(O)—(C₁-C₄-alkyl), and —SO₂—(C₁-C₄-alkyl), or Z¹ and Z² form, togetherwith the carbon atoms that they are connected to, a 5- or 6-memberedheterocycloalkyl, a 5-membered heteroaryl, or a 6-membered heteroaryl,each of which may be optionally substituted with one or two substituentsselected from the group consisting of methyl, fluorine and oxo, and Z³,Z⁴, and Z⁵ are independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, C₁-C₄-alkoxy-C(O)—, andC₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, or Z² and Z³ form,together with the carbon atoms that they are connected to, a 5- or6-membered saturated or partially saturated heterocyclic ring, a5-membered heteroaryl, or a 6-membered heteroaryl, each of which may beoptionally substituted with one or two substituents selected from thegroup consisting of methyl, fluorine and oxo, and Z¹, Z⁴, and Z⁵ areindependently selected from the group consisting of hydrogen, halogen,cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, or Qis a pyridine ring of formula (Q2)

wherein: Z⁶, Z⁷, Z⁸ and Z⁹ are independently selected from the groupconsisting of hydrogen halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, or Q is apyrimidine ring of formula (Q3)

wherein: Z¹⁰, Z¹¹ and Z¹² are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, or Q is apyridine ring of formula (Q4)

wherein: Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, —NH—CO-C₁-C₄-alkyl, and monocyclic heterocyclesselected from the group of 4- to 7-membered heterocycloalkyl or5-membered heteroaryls having at least one nitrogen atom via which theheteroaryl ring is connected to the pyridine ring, each of which isoptionally substituted with 1, 2 or 3 substituents independentlyselected from the group consisting of halogen, cyano, nitro, —OH, oxo,thiono, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms,C₃-C₆-cycloalkyl, —NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,—S—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms,—S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, and—SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or Q is apyridine ring of formula (Q5)

wherein: Z¹⁷, Z¹⁸, Z¹⁹ and Z²⁰ are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkoxy, C₁-C₄-halogenoalkoxy having 1to 5 halogen atoms, —NH(C₁-C₄-alkyl), and —N(C₁-C₄-alkyl)₂, or Q is a5-membered aromatic heterocycle of formula (Q6)

wherein: T¹-T⁴are independently selected from the group consisting of N,O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O, not morethan one of T¹-T⁴ is S, not more than one of T¹-T⁴ is N—Z²², and whereineach Z²¹ is independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, and C₁-C₄-alkoxy, and each Z²² is independently selectedfrom the group consisting of hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, andC₁-C₄-alkoxy-C₁-C₄-alkyl, or Q is a 5-membered aromatic heterocycle offormula (Q7)

wherein: U¹-U⁴ are independently selected from the group consisting of Nand C-Z²³, wherein not more than three of U¹-U⁴ are N, and wherein eachZ²³ is independently selected from the group consisting of hydrogen,halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, and C₁-C₄-alkoxy, wherein when Y is O, S or N—R⁹ is not —OH, or astereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a saltthereof, or a mixture of any of the foregoing.
 4. The compound accordingto claim 1, wherein: A is A2,

is 0, 1 or 2, R is selected from the group consisting of halogen,C₁-C₄-alkyl and C₁-C₄-alkoxy, R_(p) is selected from the groupconsisting of hydrogen and C₁-C₄-alkyl, X is selected from the groupconsisting of CR⁷R⁸, O, S, and N—R⁹, Y is CR⁷R⁸ or O, R¹ is hydrogen orC₁-C₄-alkyl, R² is selected from the group consisting of hydrogen,halogen, —C(O)—N(C₁-C₄-alkyl)₂, —NR¹²R¹³, —OR¹⁴, —SR¹⁵, —S(O)R¹⁵,—SO₂R¹⁵, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₂-C₄-alkenyl,C₃-C₆-cycloalkenyl, wherein each of the C₁-C₄-alkyl, C₃-C₆-cycloalkyl,C₂-C₄-alkenyl, and C₃-C₆-cycloalkenyl is optionally substituted by 1, 2,3, 4 or 5 substituents independently selected from the group consistingof halogen, —OH, cyano, C₁-C₄-alkoxy-C(O)— and —C(O)—NH₂C₁-C₄-alkoxy,—NH₂, —N(C₁-C₄-alkyl)₂, and —N(C₁-C₄-alkyl)(C(O)—C₁-C₄-alkyl), and amonocyclic or a bicyclic heterocycle selected from the group consistingof 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-memberedheteroaryl, and 6-membered heteroaryl, each of which is optionallysubstituted by 1, 2, 3 or 4 substituents independently selected from thegroup consisting of halogen, —OH, oxo, —COOH, C₁-C₄-alkoxy-C(O)—,—C(O)—NH₂, C₁-C₄-alkyl, C₁-C₄-alkyl-C(O)—, C₁-C₄-halogenoalkyl having 1to 5 halogen atoms, hydroxy-C₁-C₄-alkyl-, C₁-C₄-alkoxy-C₁-C₄-alkyl-,—NH₂, —N(C₁-C₄-alkyl)₂, and 4- to 10-membered heterocycloalkyl, R³ ishydrogen or C₁-C₄-alkyl, R⁴ is selected from the group consisting ofhydrogen, halogen, —OH, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1to 5 halogen atoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, R⁵ is selected from the group consisting of hydrogen,halogen, —OH, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, and C₁-C₄-alkoxy, R⁶ is selected from the groupconsisting of hydrogen, halogen, —OH, cyano, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, and C₁-C₄-alkoxy, R⁷ isselected from the group consisting of hydrogen and C₁-C₄-alkyl, R⁸ isselected from the group consisting of hydrogen and C₁-C₄-alkyl, or R⁷and R⁸ together form an oxo group (═O), R⁹ is C₁-C₄-alkyl, R¹² and R¹³are independently selected from the group consisting of hydrogen,—NH(—C(O)—C₁-C₄-alkyl), C₁-C₄-alkoxy, C₁-C₄-alkyl, C₃-C₆-cycloalkyl,phenyl-C₁-C₄-alkyl, wherein each of the C₁-C₄-alkyl, C₃-C₆-cycloalkyl,phenyl-C₁-C₄-alkyl is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of halogen, —OH, —COOH,C₁-C₄-alkoxy-C(O)—, —C(O)—NH₂, —C(O)—N(C₁-C₄-alkyl)₂,—NH—C(O)—C₁-C₄-alkyl, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₃-C₆-cycloalkyl, —NH₂,—N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl, —S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl,and (C₁-C₄-alkoxy)₂P(═O)—, heterocyclyl-C₁-C₄-alkyl, wherein theheterocyclyl substituent is selected from the group consisting of 4- to10-membered heterocycloalkyl, 5-membered heteroaryl and 6-memberedheteroaryl, each of which is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting ofhalogen, cyano, —OH, oxo, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms and C₁-C₄-alkoxy, phenyl, benzo-C₅-C₆-cycloalkyl, whereineach of the phenyl and benzo-C₅-C₆-cycloalkyl is optionally substitutedby 1, 2 or 3 substituents independently selected from the groupconsisting of halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1to 5 halogen atoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, and a monocyclic or a bicyclic heterocycle selected fromthe group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryland 6-membered heteroaryl each of which is optionally substituted by 1,2 or 3 substituents independently selected from the group consisting ofhalogen, —OH, oxo, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, C₁-C₄-alkoxy, and C₁-C₄-halogenoalkoxy having 1 to 5halogen atoms, R¹⁴ is selected from the group consisting of C₁-C₄-alkyl,C₃-C₆-cycloalkyl, phenyl-C₁-C₄-alkyl, each of which is optionallysubstituted by 1, 2 or 3 substituents independently selected from thegroup consisting of halogen, —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy andC₃-C₆-cycloalkyl, and 4- to 10-membered heterocycloalkyl, R¹⁵ isselected from the group consisting of hydrogen, C₁-C₄-alkyl, which isoptionally substituted by 1, 2 or 3 substituents independently selectedfrom the group consisting of —OH and —COOH, and a 6-membered heteroaryl,Q is a substituted phenyl ring of formula (Q1)

wherein: Z¹ and Z⁵ are independently selected from the group consistingof hydrogen, halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, andC₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, Z² and Z⁴ areindependently selected from the group consisting of hydrogen, halogen,cyano, —OH, C₁-C₄-alkyl, C₁-C₄-alkoxy, —NH(C₁-C₄-alkyl),—N(C₁-C₄-alkyl)₂, C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, —S—(C₁-C₄-alkyl) and a4- to 6-membered heterocycloalkyl, and Z³ is selected from the groupconsisting of hydrogen, halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, and —N(C₁-C₄-alkyl)₂,or Z¹ and Z² form, together with the carbon atoms that they areconnected to, a 5-membered heterocycloalkyl or a 5-membered heteroaryl,each of which may be optionally substituted with one or two substituentsselected from the group consisting of methyl, fluorine and oxo, Z³ andZ⁵ are hydrogen, and Z⁴ is selected from the group consisting ofhydrogen and C₁-C₄-alkoxy-C(O)—, or Q is a pyridine ring of formula (Q4)

wherein: Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy,C₁-C₄-hydroxyalkyl, NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂,—NH—CO-C₁-C₄-alkyl, and monocyclic heterocycle selected from the groupof 4- to 7-membered heterocycloalkyl and 5-membered heteroaryl having atleast one nitrogen atom via which the heteroaryl ring is connected tothe pyridine ring, each of which is optionally substituted with 1, 2 or3 substituents independently selected from the group consisting ofhalogen, cyano, nitro, —OH, oxo, thiono, C₁-C₄-alkyl,C₁-C₄-halogenoalkyl having 1 to 5 halogen atoms, C₁-C₄-alkoxy,C₁-C₄-halogenoalkoxy having 1 to 5 halogen atoms, C₃-C₆-cycloalkyl,—NH₂, —NH(C₁-C₄-alkyl), —N(C₁-C₄-alkyl)₂, —S—C₁-C₄-alkyl,—S(O)—C₁-C₄-alkyl, —SO₂—C₁-C₄-alkyl, —S—(C₁-C₄-halogenoalkyl) having 1to 5 halogen atoms, —S(O)—(C₁-C₄-halogenoalkyl) having 1 to 5 halogenatoms, and —SO₂—(C₁-C₄-halogenoalkyl) having 1 to 5 halogen atoms, or Qis a pyridine ring of formula (Q5)

wherein: Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and Z²⁰ is halogen, or Q is a5-membered aromatic heterocycle of formula (Q6)

wherein: T¹-T⁴are independently selected from the group consisting of N,O, S, C—Z²¹ and N—Z²², wherein not more than one of T¹-T⁴ is O, not morethan one of T¹-T⁴ is S, not more than one of T¹-T⁴ is N—Z²², and whereineach Z²¹ is independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5halogen atoms, and C₁-C₄-alkoxy, and each Z²² is independently selectedfrom the group consisting of hydrogen, C₁-C₄-alkyl, C₁-C₄-halogenoalkylhaving 1 to 5 halogen atoms, C₁-C₄-alkyl-C₃-C₆-cycloalkyl, andC₁-C₄-alkoxy-C₁-C₄-alkyl, or Q is a 5-membered aromatic heterocycle offormula (Q7)

wherein: U¹-U⁴ are independently selected from the group consisting of Nand C-Z²³, wherein not more than three of U¹-U⁴ are N, and wherein eachZ²³ is independently selected from the group consisting of hydrogen,halogen, cyano, C₁-C₄-alkyl, C₁-C₄-halogenoalkyl having 1 to 5 halogenatoms, and C₁-C₄-alkoxy, or a stereoisomer, a tautomer, an N-oxide, ahydrate, a solvate, or a salt thereof, or a mixture of any of theforegoing.
 5. The compound according to claim 1, wherein: A is selectedfrom the group consisting of

R¹ is hydrogen or methyl, R² is selected from the group consisting ofhydrogen, chlorine, iodine, —C(O)—N(CH₃)₂, —NR¹²R¹³, —OR¹⁴, —SR¹⁵,—S(O)R¹⁵, —SO₂R¹⁵, methyl, ethyl, propyl, isopropyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, propenyl, cyclopentenyl,cyclohexenyl, each of which is optionally substituted by 1 or 2substituents independently selected from the group consisting of —OH,cyano, ethoxy-C(O)—, —C(O)—NH₂, methoxy, NH₂, N(CH₃)₂, andN(CH₃)(C(O)CH₃), and a monocyclic or a bicyclic heterocycle selectedfrom the group consisting of azetidine, oxetane, pyrrolidine,tetrahydrofurane, pyrazolidine, imidazolidine, 1,2,4-triazolidine,piperidine, piperazine, tetrahydropyrane, tetrahydropyridine,dihydro-2H-pyrane, 1,2-oxazolidine, 1,2-oxazine, morpholine,thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole,1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane,6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa-3-azabicyclo[3.2.1]octane,thiophene, imidazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,3,4-tetrazole, pyridine, dihydropyridine, pyrimidine,tetrahydropyrimidine, and 4-oxa-7-azaspiro[2.5]octane, each of which isoptionally substituted by 1, 2, 3 or 4 substituents independentlyselected from the group consisting of fluorine, chlorine, cyano, —OH,oxo, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,methyl, methyl-C(O)—, difluoromethyl, trifluoromethyl, hydroxymethyl-,methoxymethyl-, —NH₂, —NMe₂, and pyrrolidine, R³ is hydrogen or methyl,R⁴ is selected from the group consisting of hydrogen, fluorine,chlorine, —OH, cyano, methyl, methoxy, trifluoromethyl, trifluoromethoxyand NH₂, R⁵ is selected from the group consisting of hydrogen, fluorine,chlorine, —OH, cyano, methyl, methoxy and trifluoromethyl, R⁶ isselected from the group consisting of hydrogen, fluorine, chlorine, —OH,cyano, methyl and methoxy, R¹² and R¹³ are independently selected fromthe group consisting of hydrogen, —NH(—C(O)-methyl), methoxy, methyl,ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl,benzyl, 1-phenylethyl, wherein each of the methyl, ethyl, propyl,isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, and1-phenylethyl is optionally substituted by 1, 2 or 3 substituentsindependently selected from the group consisting of fluorine, —OH,—COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,—C(O)—NMe₂, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH₂, NMe₂,S-methyl, S(O)-methyl, SO₂-methyl, and (EtO)₂P(═O)—,heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclylsubstituent is selected from the group consisting of oxetane,tetrahydrofurane, tetrahydropyrane, pyrrolidine, morpholine, pyrazole,imidazole, 1,2,4-oxadiazole, pyridine, each of which is optionallysubstituted by 1 substituent independently selected from the groupconsisting of fluorine, chlorine, —OH, oxo and methyl, phenyl,2,3-dihydro-1H-indene, and a monocyclic or a bicyclic heterocycleselected from the group of oxetane, thietane, pyrrolidine, morpholine,tetrahydropyrane, pyridine and pyrazole, each of which is optionallysubstituted by 1 or 2 substituents independently selected from the groupconsisting of fluorine, chlorine, —OH, oxo, and methyl, R¹⁴ is selectedfrom the group consisting of methyl, ethyl, isopropyl, butyl,cyclopentyl, and benzyl, wherein each of the methyl, ethyl, isopropyl,butyl, cyclopentyl, and benzyl is optionally substituted by 1 or 2substituents independently selected from the group consisting offluorine, —OH, methyl, methoxy and cyclopentyl, and a monocyclic or abicyclic heterocycle selected from the group consisting of pyrrolidineand tetrahydropyrane, R¹⁵ is selected from the group consisting ofmethyl, ethyl, wherein each of the methyl and ethyl is optionallysubstituted by 1 substituent independently selected from the groupconsisting of —OH and —COOH, and pyridine, Q is a substituted phenylring of formula (Q1)

wherein: Z¹ and Z⁵ are independently selected from the group consistingof hydrogen, fluorine, chlorine, methyl, trifluoromethyl and methoxy, Z²and Z⁴ are independently selected from the group consisting of hydrogen,fluorine, chlorine, —OH, cyano, methyl, ethyl, tert-butyl, —NHMe, —NMe₂,trifluoromethyl, methoxy, trifluoromethoxy, —SMe and morpholinyl, and Z³is independently selected from the group consisting of hydrogen,fluorine, chlorine, methyl, methoxy, difluoromethoxy and —NMe₂, or Q isa pyridine ring of formula (Q4)

wherein: Z¹³, Z¹⁴, Z¹⁵ and Z¹⁶ are independently selected from the groupconsisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy,ethoxy, isopropoxy, hydroxymethyl, NH₂, —NHMe —NMe₂, —NH—C(O)-Me, andmorpholinyl, or Q is a pyridine ring of formula (Q5)

wherein: Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and Z²⁰ is fluorine orchlorine, or Q is selected from the group consisting of

wherein: each Z²¹ is independently selected from the group consisting ofhydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, andmethoxy and Z²² is hydrogen or methyl, or Q is selected from the groupconsisting of

wherein: each Z²³ is independently selected from the group consisting ofhydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, andmethoxy, or Q is selected from the group consisting of

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or asalt thereof, or a mixture of any of the foregoing.
 6. The compoundaccording to claim 1, wherein: A is selected from the group consistingof

R¹ is hydrogen or methyl, R² is selected from the group consisting ofchlorine, iodine, —C(O)—N(CH₃)₂, —NR¹²R¹³, —OR¹⁴, —SR¹⁵, —S(O)R¹⁵,—SO₂R¹⁵, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl,cyclopentyl, ethenyl, propenyl, wherein each of the methyl, ethyl,propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, ethenyl, andpropenyl is optionally substituted by 1 or 2 substituents independentlyselected from the group consisting of —OH, cyano, ethoxy-C(O)—,—C(O)—NH₂, methoxy, NH₂, N(CH₃)₂, and N(CH₃)(C(O)CH₃), and a monocyclicor a bicyclic heterocycle selected from the group consisting ofazetidine, oxetane, pyrrolidine, tetrahydrofurane, pyrazolidine,imidazolidine, 1,2,4-triazolidine, piperidine, piperazine,tetrahydropyrane, dihydro-2H-pyrane, 1,2-oxazolidine, morpholine,thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole,1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo [3.3.1]nonane,6-oxa-3-azabicyclo [3.1.1]heptane, 8-oxa-3-azabicyclo [3.2.1]octane,thiophene, imidazole, pyrazole, 1,2,3-triazole, 1,2,3,4-tetrazole,pyridine, dihydropyridine, pyrimidine, and tetrahydropyrimidine, each ofwhich is optionally substituted by 1, 2, 3 or 4 substituentsindependently selected from the group consisting of fluorine, —OH, oxo,—COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH₂,methyl, methyl-C(O)—, difluoromethyl, trifluoromethyl, hydroxymethyl-,methoxymethyl-, —NH₂, —NMe₂, and pyrrolidine, R³ is hydrogen or methyl,R⁴ is selected from the group consisting of hydrogen, chlorine,fluorine, methyl, methoxy and trifluoromethyl, R⁵ is selected from thegroup consisting of hydrogen, chlorine, fluorine, —OH, cyano, methyl,trifluoromethoxy and NH₂, R⁶ is selected from the group consisting ofhydrogen, fluorine, chlorine, —OH, cyano, methyl and methoxy, R¹² andR¹³ are independently selected from the group consisting of hydrogen,—NH(—C(O)-methyl), methoxy, methyl, ethyl, propyl, isopropyl, butyl,isobutyl, cyclopropyl, cyclobutyl, benzyl, 1-phenylethyl, wherein eachof the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl,cyclobutyl, benzyl, 1-phenylethyl is optionally substituted by 1, 2 or 3substituents independently selected from the group consisting offluorine, —OH, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—,—C(O)—NH₂, —C(O)—NMe₂, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl,—NH₂, —NMe₂SO₂-methyl and (EtO)₂P(═O)—, heterocyclyl-methyl,heterocyclyl-ethyl, wherein the heterocycyl substituent is selected fromthe group consisting of oxetane, tetrahydrofurane, tetrahydropyrane,pyrrolidine, pyrazole, imidazole 1, 2, 4-oxadiazole, morpholine, andpyridine, each of which is optionally substituted by 1 substituentindependently selected from the group consisting of oxo and methyl,phenyl, 2,3-dihydro-1H-indene, and a monocyclic or a bicyclicheterocycle selected from the group of oxetane, morpholine,tetrahydropyrane, pyridine and pyrazole, R¹⁴ is selected from the groupconsisting of methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl,wherein each of the methyl, ethyl, isopropyl, butyl, cyclopentyl, benzylwhich is optionally substituted by 1 or 2 substituents independentlyselected from the group consisting of fluorine, —OH, methyl, methoxy andcyclopentyl, and a monocyclic or a bicyclic heterocycle selected fromthe group consisting of pyrrolidine and tetrahydropyrane, R¹⁵ isselected from the group consisting of methyl, ethyl, wherein each of themethyl and ethyl is optionally substituted by 1 substituentindependently selected from the group consisting of —OH and —COOH, andpyridine, Q is a substituted phenyl ring of formula (Q1)

wherein: Z¹ and Z⁵ are independently selected from the group consistingof hydrogen, fluorine, chlorine, methyl, methoxy and trifluoromethyl, Z²and Z⁴ are independently selected from the group consisting of hydrogen,fluorine, chlorine, —OH, cyano, methyl, ethyl, tert-butyl, —NHMe, —NMe₂,trifluoromethyl, methoxy, trifluoromethoxy, —SMe and morpholinyl, and Z³is independently selected from the group consisting of hydrogen,fluorine, chlorine, methyl, methoxy, difluoromethoxy and —NMe₂, or Q isa pyridine ring of formula (Q4)

wherein: Z¹⁴ and Z¹⁵ are independently selected from the groupconsisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy,ethoxy, isopropoxy, hydroxymethyl, NH₂, and morpholinyl and Z¹³ and Z¹⁶are independently selected from the group consisting of hydrogen,fluorine, chlorine, methyl, and methoxy, or Q is a pyridine ring offormula (Q5)

wherein: Z¹⁷, Z¹⁸, and Z¹⁹ are hydrogen, and Z²⁰ is fluorine, or Q isselected from the group consisting of

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or asalt thereof, or a mixture of any of the foregoing.
 7. A method ofpreparing a compound of formula (I) according to claim 1, said methodcomprising reacting an intermediate compound of formula 1N:

wherein A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined for the compound offormula (I) according to claim 1, with a compound of formula 1F:R²H   1F, wherein R² is NR¹²R¹³, OR¹⁴, or SR¹⁵, each as defined for thecompound of formula (I) according to claim 1, to give the compound offormula (I):

wherein A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined for the compoundof formula (I) according to claim 1, or reacting an intermediatecompound of formula 1T:

wherein A, R¹, R², R³, R⁴, R⁵ and R⁶ are as defined for the compound offormula (I) according to claim 1, and wherein Hal is halogen, with acompound of formula 1H:Q-B(OR)₂   1H, wherein Q is as defined for the compound of formula (I)according to claim 1, and each R may be individually H or Me or both Rare pinacolate, to give the compound of formula (I):

wherein A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined for the compoundof formula (I) according to claim 1, or reacting an intermediatecompound of formula 1W:

wherein Q, R², R³, R⁴, R⁵ and R⁶ are as defined for the compound offormula (I) according to claim 1, with a compound of formula 1M:

wherein R¹ and A are as defined for the compound of formula (I)according to claim 1, to give the compound of formula (I):

wherein A, R¹, R², R³, R⁴, R⁵, R⁶, and Q are as defined for the compoundof formula (I) according to claim 1, or reacting an intermediatecompound of formula 1X:

wherein Q, A, R¹, R³, R⁴, R⁵ and R⁶ are as defined for the compound offormula (I) according to claim 1, with a compound of formula 1Y:R²H   1Y, wherein R² is OR¹⁴ as defined for the compound of formula (I)according to claim 1, to give the compound of formula (I):

wherein A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined for the compound offormula (I) according to claim 1 and R² is C¹-C⁴-alkoxy which isoptionally substituted as defined for the compound of formula (I)according to claim 1, or reacting an intermediate compound of formula1N:

wherein Q, A, R¹, R³, R⁴, R⁵ and R⁶ are as defined for the compound offormula (I) according to claim 1, with a compound of formula 2A:R²Met-X   2A, wherein R² is C₁-C₄-alkyl, C₃-C₆-cycloalkyl,C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl or phenyl-C₁-C₄-alkyl,each of which is optionally substituted as defined for the compound offormula (I) according to claim 1, Met is magnesium or zinc, and X ischlorine, bromine or iodine, to give the compound of formula (I):

wherein A, R¹, R³, R⁴, R⁵, R⁶, and Q are as defined for the compound offormula (I) according to claim 1 and R² is C₁-C₄-alkyl,C₃-C₆-cycloalkyl, C₂-C₄-alkenyl, C₃-C₆-cycloalkenyl, C₂-C₄-alkynyl orphenyl-C₁-C₄-alkyl, each of which is optionally substituted as definedfor the compound of formula (I) according to claim
 1. 8. A compound offormula (II):

wherein: R² is —OH or as defined for the compound of formula (I)according to claim 1, R³, R⁴, R⁵, R⁶, and Q are as defined for thecompound of formula (I) according to claim 1, and R^(A) is H orC₁-C₄-alkyl, or a stereoisomer, a tautomer, an N-oxide, a hydrate, asolvate, or a salt thereof, or a mixture of any of the foregoing.
 9. Acompound of formula (III):

wherein: R² is —OH or as defined for the compound of formula (I)according to claim 1, A, R¹, R³, R⁴, R⁵, and R⁶ are as defined for thecompound of formula (I) according to claim 1, and Hal is halogen, or astereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a saltthereof, or a mixture of any of the foregoing.
 10. A pharmaceuticalcomposition comprising a compound of formula (I) according to claim 1,or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or asalt thereof, or a mixture of any of the foregoing, and one or morepharmaceutically acceptable excipients.
 11. A method for controllinghelminth infections in humans and/or animals by administering ananthelminthically effective amount of at least one compound of formula(I) according to claim 1, or a stereoisomer, a tautomer, an N-oxide, ahydrate, a solvate, or a salt thereof, or a mixture of any of theforegoing, to a human or an animal in need thereof.